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Review
. 2020 Apr 18;21(8):2839.
doi: 10.3390/ijms21082839.

COVID-19 Drug Discovery Using Intensive Approaches

Ayumu Asai  1   2   3   4 , Masamitsu Konno  1 , Miyuki Ozaki  1 , Chihiro Otsuka  1 , Andrea Vecchione  5 , Takahiro Arai  1   6 , Toru Kitagawa  1   3   7 , Ken Ofusa  1   8 , Masami Yabumoto  1   9 , Takaaki Hirotsu  1   10 , Masateru Taniguchi  2 , Hidetoshi Eguchi  1   3 , Yuichiro Doki  1   3 , Hideshi Ishii  1
Affiliations
Review

COVID-19 Drug Discovery Using Intensive Approaches

Ayumu Asai et al. Int J Mol Sci. .

Abstract

Since the infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported in China during December 2019, the coronavirus disease 2019 (COVID-19) has spread on a global scale, causing the World Health Organization (WHO) to issue a warning. While novel vaccines and drugs that target SARS-CoV-2 are under development, this review provides information on therapeutics which are under clinical trials or are proposed to antagonize SARS-CoV-2. Based on the information gained from the responses to other RNA coronaviruses, including the strains that cause severe acute respiratory syndrome (SARS)-coronaviruses and Middle East respiratory syndrome (MERS), drug repurposing might be a viable strategy. Since several antiviral therapies can inhibit viral replication cycles or relieve symptoms, mechanisms unique to RNA viruses will be important for the clinical development of antivirals against SARS-CoV-2. Given that several currently marketed drugs may be efficient therapeutic agents for severe COVID-19 cases, they may be beneficial for future viral pandemics and other infections caused by RNA viruses when standard treatments are unavailable.

Keywords: COVID-19; coronavirus; drug discovery; drug repositioning; infection.

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Conflict of interest statement

Partial institutional endowments were received from Taiho Pharmaceutical Co., Ltd. (Tokyo, Japan), Hirotsu Bio Science Inc. (Tokyo, Japan); Kinshu-kai Medical Corporation (Osaka, Japan); Kyowa-kai Medical Corporation (Osaka, Japan); IDEA Consultants Inc. (Tokyo, Japan); Unitech Co. Ltd. (Chiba, Japan).

Figures

Figure 1
Figure 1
Proposed acting points of anti-SARS-CoV-2 in the replication cycle of the virus. When SARS-CoV-2 particles bind to their receptors, such as angiotensin-converting enzyme 2 (ACE2), aminopeptidase N (APN; CD13) and dipeptidyl peptidase 4 (DPP4; CD26), viral RNA is passed to the host cell, and RNA-dependent RNA polymerase (RdRp) produces viral RNAs. During RNA methylation, the RNA cap is formed, which protects against the host innate immune response, which involves the secretion of interferons (IFNs) and cytokines (CKs). The viral (guanine-N7)-methyltransferase (N7-MTase) plays a critical role in RNA capping, using the methyl donor S-adenosyl-methionine (SAM). The process of viral RNA synthesis and the translation of proteins is associated with pH-dependent membrane stress, which can elicit adverse effects against immune and non-immune cells. If the viral replication cycle is not inhibited and infected cells are not eradicated, packed viruses will be disseminated to other cells in the host. Proposed drugs and their possible acting points against COVID-19 are shown by bold lines.
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