key: cord-341804-rnj3wtg4 authors: Jin, Zhe; Liu, Jing-Yi; Feng, Rang; Ji, Lu; Jin, Zi-Li; Li, Hai-Bo title: Drug treatment of coronavirus disease 2019 (COVID-19) in China. date: 2020-06-27 journal: Eur J Pharmacol DOI: 10.1016/j.ejphar.2020.173326 sha: doc_id: 341804 cord_uid: rnj3wtg4 Since December 2019, the coronavirus disease 2019 (COVID-19) caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spread throughout China as well as other countries. More than 8,700,000 confirmed COVID-19 cases have been recorded worldwide so far, with much more cases popping up overseas than those inside. As the initial epicenter in the world, China has been combating the epidemic for a relatively longer period and accumulated valuable experience in prevention and control of COVID-19. This article reviewed the clinical use, mechanism and efficacy of the clinically approved drugs recommended in the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (DTPNCP) released by National Health Commission of P.R.China, and the novel therapeutic agents now undergoing clinical trials approved by China National Medical Products Administration (NMPA) to evaluate experimental treatment for COVID-19. Reviewing the progress in drug development for the treatment against COVID-19 in China may provide insight into the epidemic control in other countries. ribavirin should be used in combination with alpha-interferon or lopinavir/ritonavir, 500 mg 1 per adult, 2 to 3 times per day, and be given by intravenous infusion, and the course of 2 treatment should not exceed ten days (Zehua Zhang et al., 2020). 3 Glucocorticoids are not only the most important hormones regulating stress response, but 5 also the most widely used and effective anti-inflammatory and immunosuppressant agent in 6 clinic (Allan et al., 1984) . Glucocorticoids are fat-soluble hormones that pass through the 7 cell membrane and bind to glucocorticoid receptor (GR). GR is a macromolecular complex 8 of 90 kDa, which is composed of heat shock protein (hsp90) and p59 protein. Hsp90 9 dissociates from the complex, and the activated GCS-GR complex rapidly enters the 10 nucleus, binds to the glucocorticoid response components on the target gene promoter in the 11 form of a dimer, and thus to promotes or inhibits the transcription of the target gene, and 12 finally produces pharmacological effects or side effects by regulating the gene products 13 (Wilckens and Rijk, 1997) . In addition, GCS-GR complex interacts with other transcription 14 factors such as NF-κB to inhibit the expression of inflammatory genes and directly 15 influence the gene regulation and anti-inflammation (Rhen and Cidlowski, 2005; Schäcke et 16 al., 2002) . In emergency or critical cases, glucocorticoid is often the first choice for the 17 treatment for primary or secondary (pituitary) adrenocortical dysfunction, mainly combined 18 with physiological dose of hydrocortisone or cortisone as a supplementary or replacement 19 therapy. 20 The common clinical glucocorticoids are prednisone, methylprednisone, betamethasone, 21 11 beclomethasone propionate, prednisone, prednisolone, hydrocortisone and dexamethasone 1 etc. Glucocorticoids had been used to treat SARS and MERS, resulting in lower mortality 2 and shorter hospitalization stay, and were not associated with significant secondary lower 3 respiratory infection and other complications. However, more evidence is needed either for 4 supporting or opposing the systemic therapeutic administration of glucocorticoids in 5 patients with SARS-CoV-2 infection (Qin et al., 2020 a variety of immune cells 20 and improves the immunity, while IFN-β takes effect by inhibiting the adsorption of certain 1 viruses, enhancing phagocytosis of natural killer cells and mononuclear macrophages Tocilizumab is a recombinant humanized anti-IL-6 receptor (IL-6R) monoclonal antibody, 21 13 which can specifically bind to soluble and membrane-bound IL-6 receptors and inhibit 1 signal transduction mediated by IL-6, thereby reducing inflammation and blocking cytokine 2 storm caused by COVID-19 (Scheinecker et al., 2009) . Tocilizumab was initially used in a 3 study of 21 Chinese patients with severe COVID-19 (Xu et al., 2020a) . Based on its 4 encouraging therapeutic effect, a multi-center, large-scale clinical trial 5 (ChiCTR2000029765) was further initiated, and approximately 500 severe or critically ill 6 patients were included. In the DTPNCP (Trial Version 7), tocilizumab was recommended 7 for the treatment of patients with extensive lung lesions or laboratory tests for elevated IL-6 8 levels (Antinori et al., 2020). In addition, tocilizumab combined with other drugs has been 9 applied in more than 20 countries including Italy (Toniati et al., 2020). 10 The convalescent plasma donated by patients recovered from COVD-19 contains a high 12 titer of specific antibody to SARS-CoV-2, which may mediate a strong passive immunity well tolerated, and patients who received plasma transfusion were improved in terms of 20 several parameters, including lymphocyte counts and C-reactive protein. In addition, no 1 severe adverse effects were observed (Duan et al., 2020) . Serological findings showed that 2 the plasma from six donors recovered from COVID-19 had high IgG titers (above 1:320), 3 and patients who received plasma transfusion showed no related adverse event and did not 4 require mechanical ventilation 11 days after plasma transfusion (Zhang et al., 2020b) . 5 Though several cured cases have been reported, more expanded clinical trials remains to be 6 fufilled. 7 authorization for the treatment of adults and children with severe COVID-19 disease 20 (Hendaus, 2020) . Though remdesivir was considered as a promising option for COVID-19, 21 17 its safety and effect in humans still requires more evidence from additionalclinical trials (Li 1 et al., 2020). Abundant studies on acute lung injury caused by highly pathogenic viruses, such as 2 influenza A virus and coronavirus, have found that overactivation of complement 3 (especially C5a) may be the central event in that process (Wang et al., 2015) . Therefore, C5a 4 is highly valued as a rational target for the treatment of highly pathogenic virus-mediated 5 acute lung injury. Most of the promising drugs described above are small molecule drugs, but biological 8 products with specific targeting abilities and less side effects are gradually attracting 9 interests. The mechanisms underlying the therapies for COVID-19 that have been approved 10 for clinical use or are being evaluated in clinical trials include blocking viral replication, 11 regulation of immune function, reducing inflammatory response and alleviating lung 12 injury (Table 1) Medical University) for their linguistic assistance during the revison of this manuscript. 11 The authors declare no competing interests. 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