key: cord-340042-intxyu46
authors: Chaudhry, Sundas Nasir; Hazafa, Abu; Mumtaz, Muhummad; Kalsoom, Ume; Abbas, Saima; Kainaat, Amna; Bilal, Shahid; Zafar, Nauman; Siddique, Aleena; Zafar, Ayesha
title: New insight on possible vaccine development against SARS-CoV-2
date: 2020-09-11
journal: Life Sci
DOI: 10.1016/j.lfs.2020.118421
sha: 
doc_id: 340042
cord_uid: intxyu46

In December 2019, a novel virus, namely COVID-19, caused by SARS-CoV-2, developed from Wuhan, Hubei territory of China, which used its viral spike glycoprotein receptor-binding domain (RBD) for the entrance into a host cell by binding with ACE-2 receptor and cause acute respiratory distress syndrome (ARDS). Data revealed that the newly emerged SARS-CoV-2 affected more than 24,854,140 people with 838,924 deaths worldwide. Until now, no licensed immunization or drugs are present for the medication of SARS-CoV-2. The present review aims to investigate the latest developments and discuss the candidate antibodies in different vaccine categories to develop a reliable and efficient vaccine against SARS-CoV-2 in a short time duration. Besides, the review focus on the present challenges and future directions, structure, and mechanism of SARS-CoV-2 for better understanding. Based on data, we revealed that most of the vaccines are focus on targeting the spike protein (S) of COVID-19 to neutralized viral infection and develop long-lasting immunity. Up to phase-1 clinical trials, some vaccines showed the specific antigen-receptor T cell response, elicit the humoral and immune response, displayed tight binding with human-leukocytes-antigen (HLA), and recognized specific antibodies to provoke long-lasting immunity against SARS-CoV-2.

Immune Medical Institute), and INO-4800 (Inovio) presenting the significant results in initial trials and soon will be tested on human [27] . Spike protein (S) of coronavirus are targeted by these vaccines and help in the stimulation of neutralizing antibodies [28] . Different subunits of spike proteins like the S1 and S2 subunits, and the receptor-binding domain (RBD) are the critical elements for the formation of a vaccine against the newly emerged virus that helped in producing T cell responses and protective immunity against SARS-CoV-2 [29] .

Furthermore, two recombinant proteins that carry a receptor-binding domain (see glossary), and recombinant vectors that code for the receptor-binding domain can also play a useful role in developing a corona-vaccine. Besides, the monoclonal antibodies of recovered corona-patients showing better results in neutralizing the antibodies by targeting the specific domains of SARS-CoV-2 [30, 31] . However, with increasing the cases and deaths of COVID-19 day by day, the development of vaccines against SARS-CoV-2 is also required on an urgent basis. The present review investigated the new insight parameters and components to develop a vaccine against newly emerged COVID-19 by targeting the spike protein and epitopes. The present study also aims to share the candidate antibodies and latest development in the formulation of a vaccine against SARS-CoV-2. Further, current challenges and future perspectives, the structure, mechanism, immune response, and different components of COVID-19 are studied in the present review for a better understanding. cathepsins B and L in SARS-CoV-2 [40] . The evidence revealed that the cellular protease, like TMPRSS2 (see glossary) plays an essential role during the entry and circulation of SARS-CoV-2. However, the antiviral or vaccine could be a potential therapeutics against COVID-19 by blocking the regulation of TMPRSS2 enzyme [41] . However, the entry of the virus is cell type and protease specific dependent. Six HBs are framed by the communication of heptad repeats 1 and 2 (HR1 and HR2), and the areas present in a spike protein formed by the embedment of peptides in the layer of endosomes [42] . As a result, an envelope of virus and plasma film is synthesized by the Golgi intermediate compartment. Finally, the newly formed virus RNA genome is discharged from the cell through exocytosis. The detailed pathway is presented in Fig.   2 . To reduce the binding of virus with the host receptor known as ACE2, the subunit immunizations for both SARS coronaviruses depend on inspiring a resistant reaction contrary to the spike protein [43] .

To prevent the viral infection, there is a need for the natural killer cells to perceive the entrance of the virus into a host cell. According to accumulated data, only limited researches are presented yet on the innate immune response to SARS-CoV-2 infection. Recently, an ongoing project (consist of 35 cases) in Buali Hospital, Iran revealed a significant reduction of 45% (1100 u/L) in lymphocytes, improvement in total neutrophil (48%), C-reactive protein (99%), and serum IL-6 (58%). The results also reported that the amount of lymphocytopenia and neutrophilia are correlated with infection mortality and disease severity [13, 44] . Similarly, another report based on 99 cases in Wuhan, China, claimed the 35% reduction in total lymphocytes, 38, 84, and 52% enhancement in neutrophils, C-reactive proteins, and serum IL-6, respectively [45] . The immune responses associated with the diseases of the lung may have resulted in a large amount of J o u r n a l P r e -p r o o f cytokines (see glossary) production, which provides the 1 st line defense against viral infection [46] . In addition, the humoral cells of the body are responsible for antibodies production against viral, which could play a significant role in preventing viral infection by killing them [47] . The innate immune system could effectively identify the situation during the incursion of the virus, usually called pathogen-associated molecular patterns (PAMPs). However, the endosomal RNA receptors, RIG, cytosolic RNA sensor, TLR7, and TLR8 quickly recognized these PAMPs (present in the form of ssRNA on the viral genome) during the replication of the virus and cause stimulation of numerous signaling pathways and transcription factors including NF-κB, IRF-3, AP-1 and IRF-7 [48, 49] . Ultimately, these nuclear factors, especially AP-1 and NF-κB, activated the expression of genes that encoded the chemokines (CXCL8 and CCL2), and cytokines (IL-1 and TNF) that lead to the inflammatory responses. Similarly, other nuclear factors, namely IRF3 and IRF7, increased the production of INF-type 1 (IFNα and INFβ), which significantly helped in the reduction of viral dissemination and replication (see Fig. 3 ) [50] .

Based on the increasing incidences of newly emerged COVID-19, there is necessary to make a successful and safe vaccine against SARS-CoV-2 to control its present pandemic and future recurrence. The present lethal coronavirus (COVID-19) shared the structure homology with previously reported beta-coronaviruses, including MERS-CoV (50%) and especially SARS-CoV (79.6%) [27] . Based on their structure homology, the genome accession number (GenBank), [51] . Accumulated data reported that the formation of a vaccine falls into one of the following types; viral vectors (25 projects and one is under clinical trial), DNA and mRNA-J o u r n a l P r e -p r o o f based (20 projects and one from each type is under clinical trial), protein-based (28 projects and mostly on S protein), virus-like particle (VLP) (5 projects), inactivated or live-attenuated virus (7 projects and two are under clinical trial), and epitope vaccine [52, 53] . Antibodies are the best and conservative means to anticipate and control desirable infections. Till more than 40 pharmaceutical industries and scholarly foundations all over the world have propelled their plans on immunization improvement against SARS-CoV-2 [54] . Herein, we discussed the new insights and latest developments in each class of vaccines to formulate a strong and effective vaccine against SARS-CoV-2.

The vaccine development gained special attention during the last few decades, including the development of RNA, DNA, and protein-based vaccines against several viruses like the influenza virus, and Ervebo virus. The proteins are the important constituents in the structural activities of coronavirus, which are involved in the transmission, entry, and replication of viruses. The data suggested that proteins could be ideal targets for the development of vaccines [13, 55] . The emerging evidence revealed that the viral spike (S) protein vaccine showed the higher neutralizing titers (see glossary) against SARS-CoV than other vaccine candidates. Based on accumulated data, the S protein is the preferred site of vaccine formation against previously emerged coronaviruses (MERS and SARS-CoVs) because S protein could easily be encountered and allow the body to make an immune response more efficiently than other proteins [55, 56] .

Based on these points, the potential parts of S protein, which are used as antigens in immunization improvement, integrate the entire extent of this protein and vaccine development [57] . Pallesen et al. [58] reported that the S ectodomain of coronavirus with G4 showed a glycosylated loop variation in a structure of the virus, and observed the four major J o u r n a l P r e -p r o o f conformational sites in a trimer for the binding of each RBD either relatedly or tightly to a receptor accessible confirmation. However, the structure-based design of coronavirus could provide a prospective way for the formulation of a vaccine.

Many pharmaceutical industries and universities start working for the development of vaccines against COVID-19. Recently, the AstraZeneca and the University of Oxford began to combined effort to develop a spike protein (S) vaccine, namely AZD1222 against newly emerged SARS-CoV-2 in chimpanzee to generate the DNA for the spike antigen and to grow the vigorous T cell and B cell responses for better prophylaxis with less dose [59] . Besides, another company who made a vaccine against Ebola virus, namely CanSino Biologics (China) started a project to create a safe and efficient S protein antigen-based vaccine (Ad5-nCoV) against SARS-CoV-2 that is undergoing the phase-1 clinical trial on individuals aged between 18-60 years under ClinicalTrial.gov: NCT04313127 [60] . Similarly, the two top vaccine producer companies, including GlaxoSmithKline and Sanofi start working on the formation of spike protein-based vaccine against COVID-19 to trigger the immune response, and they reported that they would begin phase-1 clinical trials later this year [59] .

Besides, the subunits of S protein, including receptor-binding domain (RBD), N-terminal domain (NTD), and C-terminal domain (CTD) also consider as a vital target for the progress of a vaccine. The study reported that antibodies that are attached to the N-terminal domain of the S1 subunit of coronavirus demonstrated an active killing movement, which indicates that NTD is applicable in balance for vaccine development. Jiaming and his research group [61] experimented on BALB/c immunized mice at two different doses (5 and 10 µg) to investigate the effect of recombinant NTD (rNTD) for vaccine development and immunogenicity. They revealed that high administration of 10 µg significantly reduced the lung infection caused by a J o u r n a l P r e -p r o o f coronavirus in a recombinant vaccinated mouse model. They also observed a robust T-cell immune retort in the serum of vaccinated mice (rNTD) with CpG and aluminum adjuvant. Geo et al. [62] experimented on BALB/c mice (n=9) to check the RBD, S, and N-protein antibody response after 1-6 weeks of first immunization at 6 µg dose (accessed by ELIZA). They observed that SARS-CoV-2 linked RBD and S-protein immunoglobulin G (IgG) (see glossary)

instantly start to develop inside the immunized mice at 6 th week with the peak titer of 409,600 (100 µg/mL) and 819,200 (200 µg/mL) respectively.

Interestingly, the peak titer of N-specific IgG in antibody response was about 30 times fewer than RBD in vaccinated mice. But recently, another study stated that the N-specific IgG is reported as one of the most effective proteins in COVID-19 recovered patients as a diagnostic marker and vaccine development [63] . The study revealed that the RBD of specific IgG showed about the half of the value of antibody response than S protein, and suggested that the RBD is a meticulously associated immunogen to the recovered patients of COVID-19 [62] . However, the S protein and RBD of SARS-CoV-2 might be an innovative possible target for the formulation of the vaccine.

The inactivated vaccine (known as Whole Killed Virus: WKV) is an important vaccine that possesses the ability to cease the replication cycle of the virus, and it is generally prepared by neutralizing the virus through radiation or heat, and chemicals like formaldehyde. According to emerging evidence, the inactivated virus vaccine is one of the safe and effective vaccines, which can easily be prepared with much fewer cost as compared to nucleic acid vaccines [64] . The WKV vaccine could significantly target the subunits of viruses, including S and E proteins, ORF, matrix (M), and boost the immune response against viruses [65] . The WKV vaccine has attained J o u r n a l P r e -p r o o f special attention over the decades due to its several advantages against viruses, particularly SARS-CoV, that could easily neutralize the virus antibodies [64] . Most recently, a study experimented on non-human primates (rhesus macaques), rat, and mice (BALB/c) at two different doses (3 and 6 µg) for the investigation of protective potential and immunogenicity of purified inactivated virus vaccine candidate (PiCoVacc). They revealed that PiCoVacc significantly neutralized the effect of ten SARS-CoV-2 strains and demonstrated the partial or complete protective potential against SARS-CoV-2 in macaques deprived of any development of the antibody-dependent disease. The data suggested that the inactivated virus vaccine candidate (PiCoVacc) could be proved as a novel option for a vaccine development against COVID-19 [62] . Another study demonstrated that inactivated virus vaccine also showed a protective behavior against previously emerged coronavirus, namely SARS-CoV-1, but phase-1 clinical trials were dried due to several reasons including a low number of cases and lack of funds, but few neutralizing monoclonal antibodies (see glossary) development by inactivated virus vaccine like CR3022 that could be a potent cross-protection against COVID-19 [55, 66] .

Based on the accumulated data, the live attenuated and inactivated virus vaccines are reported as one of the safest and effective vaccines against previously emerged viruses, namely influenza virus [67] . The live attenuated virus vaccine could be developed by diagnosing the newly emerged transmitted SARS-CoV-2 through a possible fewer risk of pathogenesis like enhanced anti-inflammatory cytokines, minimum lung infection, and fewer neutrophil influx as compared to wild type virus [51] . The inactivated and live attenuated virus vaccines consider the whole virus as a vaccine. A study evaluated the performance of live attenuated vaccine, by initiating alteration (Y6398H) into Orf1a/b polyprotein (nsp14) of mice, which showed the significant replication reduction behaviors of coronavirus in mice after day five intracerebral inoculation J o u r n a l P r e -p r o o f [52] . Similarly, a recent study suggested that the development of oral live attenuated virus vaccine could be a potential target to diminish the lung infections triggered by SARS-CoV-2, due to its initial infection in guts which resultingly boosted up the mucosa that associated with immune system during the early immune response against COVID-19 [68] . Another study also reported that the live attenuated virus vaccine could easily be administrated and serve as a community spread to rapidly develop herd immunity against the pathogens of COVID-19 [69] . against SARS-CoV-2 that is under phase-1 clinical trial [70] . However, few limitations could also be manifested during the expansion of inactivated or live attenuated vaccines against SARS-CoV-2. First, the live attenuated vaccines could regain its virulent effect in an in vivo or cell culture. Second, the coronavirus could prevent seepage from the immunity developed by these vaccines through quick progression. Thus, the manufacturer should be aware and careful during the development of these (inactivated and live attenuated) vaccines against SARS-CoV-2 [71]. 

Antibodies that are made up of DNA contained circular DNA molecules that encoding at least one foreign particle, and these antibodies are considered as better, as compared to other antibodies [77, 78] . The DNA-based vaccine could effectively target several variants of coronavirus including the S1 domain, and prefusion stabilized ectodomain with furring cleavage, spike protein, receptor-binding domain (RBD), cytoplasmic tail, and transmembrane domain [79, 80] . The DNA-based vaccine composition is an expensive and sophisticated method, which consists of double-stranded plasmids that are usually designed with the help of a computer/smart device to generate an immune retort against the virus. A specific device, named CELLECTRA is used to generate the electric pulse under the skin to usher the DNA-based vaccine [81, 82] . The results revealed no serious adverse effect and immune response was dose-dependent, at 6 mg the candidates showed the maximum immune response against MERS-CoV. However, future study is required to check the efficiency of DNA-based vaccine (DLS-5300) against newly emerged SARS-CoV-2, that could be a novel target.

The previously reported studies revealed that the computation strategy is one of the effective techniques for the development of vaccines against many lethal infections, including malaria, cancer, and dengue. This technique worked by recognition of novel T cell epitopes, and MHC 1 and 2 molecules (see glossary) for the development of specific vaccines associated with the Transporter of Antigen Presentation (TAP) agents [86, 87] . This vaccine is made up of antibodies related to the segments of immaculate foreign particles and is generally arranged by J o u r n a l P r e -p r o o f substance amalgamation procedures. These antibodies are simpler in readiness and also have efficient control [88] . Based on its previous tremendous application in other diseases like dengue, the epitope-based virus could be an essential option in the formulation of vaccines against SARS-CoV-2. Currently, many projects are undergoing vaccine formation. Khan 

Subunit immunizations include at least one antigen with solid immunogenicity to prepared to efficiently vaccine that activates the host immune system. This kind of antibody is more secure and simpler to create because it did not contain any live virus for the development of a vaccine.

However, it frequently requires the development of adjuvants (see glossary) to induce a solid defensive safe reaction. But like other vaccines like inactivated or live attenuated vaccine, the subunit vaccine is less immunogenic that could be improved by adding the suitable adjuvants [92, 93] . Up until few foundations have started working on the formulation of a subunit-based vaccine to target the virus. The University of Queensland has begun work to build up this type of subunit body, which depends upon the molecular lamp methodology [94] .

Similarly, Clover Biopharmaceuticals Inc. started the initial validation in building up an antibody competitor against SARS-CoV-2 by utilizing the "Trimer-Tag" innovation [95] . Liu and his research group designed a novel S1-subunit based nano-vaccine against SARS-CoV-2 and stated that nano-vaccine showed the strong immune and humoral response and effectively elicited the T-cell response by triggering CD4 + and CD8 + cells, which to minimize the viral load in affected persons. The results also revealed that the nano-vaccine provoke the IgA antibody, which provides the mucosal protection against viral load [96] . Kalita 

The recombinant protein is known as one of the emerging fields for the development of a vaccine against viruses due to several properties including tight binding to specific ACE-2 receptor, provoke immune protection against viral infections, increase antibody-dependent viral entry, and promote antigenicity against virus like SARS-CoV [52] . The accumulated data stated that the recombinant ACE-2 (rACE-2) receptor exerted the potential targets against the protection of many diseases, including acute Ang 2-induced hypertension, and severe lung injury [98, 99] .

Besides, rACE-2 showed the rapid cure rate with a half-life of about 60 min in mice as well as humans [100] . Lei et al. [101] suggested that this vaccine could be a new hope against newly emerged SARS-CoV-2 due to structure homology with SARS-CoV-1 [102] . Table 1 illustrates some essential vaccine candidates that are presently under clinical trials for the formulation of an active vaccine against the pandemic of SARS-CoV-2. In contrast, Fig. 4 explained the general mechanism of action of different vaccines to provoke the humoral and immune retort against SARS-CoV-2.

J o u r n a l P r e -p r o o f

Based on the present pandemic situation caused by newly emerged SARS-CoV-2, there is a need to make a vaccine on urgent bases. After examination, it is revealed that the calculated Ro value of SARS-CoV-2 is 2.2. This indicates that one contaminated person could contaminate more 2.2 persons. However, by using different precautionary measures, isolation, and quarantine activities, the Ro value could be decreased [103] . No doubt, the vaccine formulation process is not only expensive and time taking but also very complicated that sometimes gives a very low success rate. Currently, more than 40 pharmaceutical industries and various international institutes are working for the development of several types of vaccines. Still, all are under phase-1 clinical trials, and no vaccine has been licensed yet [104] . Vaccines elicit the immune response against viruses, but currently, one of the major concerns is that no one knows what kind of immune response is required against SARS-CoV. One of the basic alarms is the disadvantages of several vaccines, including the unstable under physiological condition, low immunogenicity, organ failure, required high dose, and more adjuvants. However, these disadvantages need to be addressed and improved on urgent bases in the next version of vaccine development [105, 106] .

However, the delivery of vaccine both in immunization and modality modes are also significant issues which also needs to be revised to minimize the off-target effects. Based on data, it is suggested that the aerosol route or oral administration could be a better way for vaccine delivery that might significantly induce a mucosal response.

Similarly, DNA plasmid or vector could also be used for the delivery of the vaccine to its target site [51, 107, 108] . Previously due to negligence and improper attention of government towards this task, no proper improvement in vaccine development is seen especially against MERS and SARS-CoVs. The government and health departments do not have a proper budget to manage it.

In 20 years the SARS-CoV is considered to be 3 rd epidemic war [7] .

Based on accumulated data, we suggested that the development of the ideal vaccine should possess some major properties, including 1) the perfect vaccine should be well-coordinated and strongly elicit the T-lymphocyte immunity that could lead to the stimulation of cytotoxic T- 

Based on the increasing incidences of COVID-19, there is urgently needed to formulate a vaccine against SARS-CoV-2. Based on emerging evidence, we recommended several vaccine categories including subunits, epitopes, mRNA, protein, especially S protein, recombinant adenovirus, and fusion proteins, inactivated and live attenuated virus for the formulation of a timely required vaccine against SARS-CoV-2. More than 40 pharmaceutical industries and institutes are started works on more than 100 projects for the development of different vaccines against COVID-19. These vaccines significantly neutralized the SARS-CoV-2 and developed a strong immune and humoral response against the virus. We suggested that the receptor-binding J o u r n a l P r e -p r o o f domain (RBD), a component of S protein, might show a noteworthy role in neutralizing the antibodies because it inhibits the entrance of the virus into the host by blocking the attachment of the virus to the host membrane and also block the virus membrane fusion which could help in vaccine development. But the site-specific glycan defense creates difficulties in targeting the specific antigen. However, the vaccine development will be a challenging task, and it did not guarantee the success against SARS-CoV-2, because no efficient and reliable vaccine is developed yet against the AIDS/HIV even after the 30 years of occurrence. It is recommended that further study is needed to discover the more target sites instead of to only S protein for better inside into understanding and also suggested that Cryptic epitopes based studies should be conducted on urgent bases to identify more antibody targets to generate a better long-lasting and stable immunity against SARS-CoV-2. 

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

For this type of study informed consent is not required. 

COVID-19 spike-host cell receptor GRP78 binding site prediction

Presumed asymptomatic carrier transmission of COVID-19

Overlapping and discrete aspects of the pathology and pathogenesis of the emerging human pathogenic coronaviruses SARS-CoV, MERS-CoV, and 2019-nCoV

A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)

Hospitalization rates and characteristics of patients hospitalized with laboratoryconfirmed coronavirus disease 2019-COVID-NET, 14 States

A systematic review of COVID-19 epidemiology based on current evidence

The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak

The broad-spectrum antiviral recommendations for drug discovery against COVID-19

Clinical features of patients infected with 2019 novel coronavirus in

The trinity of COVID-19: immunity, inflammation and intervention

Emerging coronaviruses: genome structure, replication, and pathogenesis

COVID-19 in Singapore-current experience: critical J o u r n a l P r e -p r o o f Journal Pre-proof global issues that require attention and action

A new coronavirus associated with human respiratory disease in China

A review of coronavirus disease-2019 (COVID-19)

A novel coronavirus from patients with pneumonia in China

Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission

COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses

Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov

A pilot clinical trial of recombinant human angiotensin-converting enzyme 2 in acute respiratory distress syndrome

Cleavage and activation of the severe acute respiratory syndrome coronavirus spike protein by human airway trypsin-like protease

Situation Report

Patients of COVID-19 may benefit from sustained lopinavir-combined regimen and the increase of eosinophil may predict the outcome of COVID-19 progression

Green synthesis and biological evaluation of novel 5-fluorouracil derivatives as potent anticancer agents

Assessment of knowledge, attitude and practice of adverse drug reaction reporting among healthcare professionals in secondary and tertiary hospitals in the capital of Pakistan

Engineering a stable CHO cell line for the expression of a MERScoronavirus vaccine antigen

Phylogenetic analysis and structural modeling of SARS-CoV-2 spike protein reveals an evolutionary distinct and proteolytically-sensitive activation loop

A fusion peptide in the spike protein of MERS

mRNA vaccines-a new era in vaccinology

Preliminary identification of potential vaccine targets for the COVID-19 coronavirus (SARS-CoV-2) based on SARS-CoV immunological studies

Adjuvant system AS01: helping to overcome the challenges of modern vaccines

Genome composition and divergence of the novel coronavirus (2019-nCoV) originating in China

Cryo-EM structure of the SARS coronavirus spike glycoprotein in complex with its host cell receptor ACE2

Cryo-electron microscopy structure of a coronavirus spike glycoprotein trimer

Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine

Structure of mouse coronavirus spike protein complexed with receptor reveals mechanism for viral entry

Receptor recognition by the novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS coronavirus

Public health responses to COVID-19 outbreaks on cruise ships-worldwide

Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses

Host cell proteases: Critical determinants of coronavirus tropism and pathogenesis

COVID-19: Coronavirus replication, pathogenesis, and therapeutic strategies

Structural basis of receptor recognition by SARS-CoV-2

Vaccination against Toxoplasma gondii: an increasing priority for collaborative research?

Immune responses and pathogenesis of SARS-CoV-2 during an outbreak in Iran: Comparison with SARS and MERS

A pneumonia outbreak associated with a new coronavirus of probable bat origin

Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology

Immune responses in COVID-19 and potential vaccines: Lessons learned from SARS and MERS epidemic

Coronavirus infections and immune responses

SARS and MERS: recent insights into emerging coronaviruses

Coronavirus endoribonuclease activity in porcine epidemic diarrhea virus suppresses type I and type III interferon responses

The outbreak of SARS-CoV-2 pneumonia calls for viral vaccines

Research and development on therapeutic agents and vaccines for COVID-19 and related human coronavirus diseases

The race for coronavirus vaccines: a graphical guide

The socio-economic implications of the coronavirus and COVID-19 pandemic: a review

SARS-CoV-2 vaccines: status report

Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor

Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor

Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen

COVID-19 vaccine development pipeline gears up

SARS-CoV-2/COVID-19: Viral genomics, epidemiology, vaccines, and therapeutic interventions

The recombinant N-terminal domain of spike proteins is a potential vaccine against Middle East respiratory syndrome coronavirus (MERS-CoV) infection

Development of an inactivated vaccine candidate for SARS-CoV-2

A preliminary study on serological assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 238 admitted hospital patients

Vaccination strategies to combat novel corona virus SARS-CoV-2

The ORF7b protein of severe acute respiratory syndrome coronavirus (SARS-CoV) is expressed in virus-infected cells and incorporated into SARS-CoV particles

Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody

Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices-United States, 2019-20 influenza season

An oral live attenuated vaccine strategy against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2/2019-nCoV)

Evolution and containment of transmissible recombinant vector vaccines

Progress and prospects on vaccine development against SARS-CoV-2, Vaccines

Potential of live pathogen vaccines for defeating the COVID-19 pandemic: history and mechanism

mRNA as a transformative technology for vaccine development to control infectious diseases

Optimization of lipid nanoparticles for intramuscular administration of mRNA vaccines

Race for a Coronavirus Vaccine: Thanks in part to institutional support

Moderna Therapeutics, and other developers are exploring diverse approaches against SARS-CoV-2

SARS-CoV-2 mRNA Vaccine Development Enabled by Prototype Pathogen Preparedness

Leveraging mRNAs sequences to express SARS-CoV-2 antigens in vivo

The novel coronavirus originating in Wuhan, China: challenges for global health governance

Pre-fusion structure of a human coronavirus spike protein

A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice

Characterization and preclinical evaluation of the cGMP grade DNA based vaccine, AV-1959D to enter the first-in-human clinical trials

Engineering DNA vaccines against infectious diseases

DNA vaccine protection against SARS-CoV-2 in rhesus macaques

Immunogenicity of a DNA vaccine candidate for COVID-19

Safety and immunogenicity of an anti-Middle East respiratory syndrome coronavirus DNA vaccine: a phase 1, open-label, single-arm, doseescalation trial

Design of a heterosubtypic epitope-based peptide vaccine fused with hemokinin-1 against influenza viruses

The role of the proteasome in generating cytotoxic T-cell epitopes: insights obtained from improved predictions of proteasomal cleavage

A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster

Design of an Epitope-Based Peptide Vaccine against the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2): A Vaccine Informatics Approach

Application of in-silico reverse vaccinology for designing multiepitope vaccine against Coronavirus

Multi-epitope vaccine design using an immunoinformatics approach for 2019 novel coronavirus in China (SARS-CoV-2), bioRxiv

The latest advancements in Zika virus vaccine development

The Potency of an Anti-MERS Coronavirus Subunit Vaccine Depends on a Unique Combinatorial Adjuvant Formulation

The SARS-CoV-2 vaccine pipeline: an overview, Current tropical medicine reports

Clover initiates development of recombinant subunit-trimer vaccine for wuhan coronavirus

A translatable subunit nanovaccine for COVID-19

Design of a peptide-based subunit vaccine

Angiotensin-converting enzyme 2 protects from lethal avian influenza A H5N1 infections

Angiotensin-converting enzyme 2 inhibits lung injury induced by respiratory syncytial virus

Pharmacokinetics and pharmacodynamics of recombinant human angiotensin-converting enzyme 2 in healthy human subjects

Potent neutralization of 2019 novel coronavirus by recombinant ACE2-Ig

Protection of Rhesus Macaque from SARS-Coronavirus challenge by recombinant adenovirus vaccine

Comparative replication and immune activation profiles of SARS-CoV-2 and SARS-CoV in human lungs: an ex vivo study with implications for the pathogenesis of COVID-19

Potential rapid diagnostics, vaccine and therapeutics for 2019 novel coronavirus (2019-nCoV): a systematic review

A decade after SARS: strategies for controlling emerging coronaviruses

New vaccine technologies to combat outbreak situations

Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia

Safe staphylococcal platform for the development of multivalent nanoscale vesicles against viral infections

A Snapshot of the Global Race for Vaccines Targeting SARS-CoV-2 and the COVID-19 Pandemic

Rapid COVID-19 vaccine development

S National library of Medicine

SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor

Infection and rapid transmission of SARS-CoV-2 in ferrets