key: cord-253990-m75xwrz9
authors: Wang, Zhiguo; Hong, Xiaojing; Wang, Hongyan; Liu, Jun; Liu, Jun‐Ping
title: Covid‐19: From structure to therapeutic targeting in studying approved drugs and local DNA vaccination
date: 2020-10-29
journal: Clin Exp Pharmacol Physiol
DOI: 10.1111/1440-1681.13409
sha: 
doc_id: 253990
cord_uid: m75xwrz9

The coronavirus disease 2019 (COVID-19) pandemic presents an unprecedented threat to global public health. The spread of the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infections in a global scale has affected more than 30.6 million people suffering the COVID-19, resulting in more than 955,000 deaths globally as of the 20 September 2020. The current lack of specific and effective therapies for the COVID-19, and the continuous spread of coronavirus SARS-CoV-2 across many parts of the world, represent one of the major challenges in controlling the disease severity, keeping to pose a huge threat to the global health.

The coronavirus disease 2019 (COVID-19) pandemic presents an unprecedented threat to global public health. The spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections on a global scale has affected more than 30.6 million people suffering the COVID-19, resulting in more than 955 000 deaths globally as of the 20 September 2020. The current lack of specific and effective therapies for the COVID-19, and the continuous spread of coronavirus SARS-CoV-2 across many parts of the world, represents one of the major challenges in controlling the disease severity and consequences, posing a huge threat to the global health. In this article, we highlight several previously approved drugs for potential effect on combating SARS-CoV-2 coronavirus infection, and modulating pulmonary inflammation and immune response.

Despite unprecedented efforts to contain the virus spread and prevent infection, SARS-CoV-2 pneumonitis can still rapidly strike to incapacitate the lung causing severe acute respiratory distress syndrome (ARDS), resulting in severe disease aftermath and sometimes death. 1 Similar to the SARS virus and dissimilar to the seasonal influenza virus, SARS-CoV-2 causes the high rates of mortality in COVID-19 patients without evident immunodeficiency, and sequelae of survivors, instigating panic in the general population. 2 Therefore, as currently highest challenges in medical cares, identifying existing treatments that can be quickly and effectively repurposed to reduce morbidity and mortality, in addition to creating immune vaccine, has led to an explosion of enormous interest in combating COVID-19.

To repurpose drugs for a faster, as well as far more economical, effect than starting development from scratch on COVID-19, recent studies by Xiao-Jing Zhang and colleagues demonstrated in a retrospective cohort study that statin use has a beneficial effect on COVID-19. 3, 4 The authors have found a significantly reduced risk of mortality in COVID-19 patients having statin therapy, with the risk for 28-day all-cause mortality being 5.2% in the matched statin group and 9.4% in the matched non-statin group (P = .001) 3 While the mechanism of statin action on COVID-19 requires investigation, it has been noted that statins potentially withhold the host's immune system and attenuate a 'cytokine storm', which likely imposes the greatest risk of death. 4 Previous studies showed that statins suppress TLR4/MyD88/NF-kB signalling and modulate the NLRP3 inflammasome. 5 In addition, statins modulate pro-inflammatory cytokine release such as interleukin-6 and interleukin-8, [6] [7] [8] [9] which are considered to be the potential drivers of the COVID-19 'cytokine storm' or cytokine release syndrome to cause ARDS. 4 sion, which is a key step in inflammatory infiltration. 11 Pre-treatment with nicorandil (100 µg/kg⋅hour) has also been showen to prevent non-ventilated lung collapse and protect re-expansion in one-lung ventilation in rabbit model. 11 In addition, nicorandil effectively protects rat lung from ischaemic injury, with the drug decreasing the extent of pulmonary microvascular permeability in 60 minutes of reperfusion in association with reduced filtration coefficient and the wet-to-dry lung weight ratio. 11 Furthermore, nicorandil has been shown to improve the levels of cyclophosphamide-induced lung fibrosis, silica-induced lung inflammation and fibrosis, and bleomycin-induced lung fibrosis in different animal models. 11 Notably, about one-third of the Middle East Respiratory Syndrome-related coronavirus (MERS-CoV) and the old SARS-CoV cases were associated with the radiological findings of lung fibrosis, and SARS-CoV-2 infection has a high tendency for pulmonary parenchymal and interstitial fibrosis. 11 F I G U R E 1 Structures of three quercetin complexes with two SARS-CoV-2 viral proteins, and the viral protein receptor ACE2. Quercetin is shown in a sphere model (the carbon, oxygen and hydrogen atoms are in grey, red, and white colours respectively). ACE2 (PDB 1R4L) and SARS-CoV-2 3CL protease (PDB 6M2N) are shown in khaki and cyan ribbons, respectively. The three chains (A, B, and C) of the SARS-CoV-2 spike glycoprotein (PDB 6VSB) are in khaki, cyan, and plum colours, respectively

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This work was supported by grants from the National Natural Science