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Review
. 2020 Jun 11;6(6):1283-1295.
doi: 10.1016/j.chempr.2020.04.023. Epub 2020 May 22.

Chemistry and Biology of SARS-CoV-2

Alexander Dömling  1   2 , Li Gao  1
Affiliations
Review

Chemistry and Biology of SARS-CoV-2

Alexander Dömling et al. Chem. .

Abstract

SARS-CoV-2 (previously 2019-nCoV or Wuhan coronavirus) caused an unprecedented fast-spreading worldwide pandemic. Although currently with a rather low mortality rate, the virus spread rapidly over the world using the modern world's traffic highways. The coronavirus (CoV) family members were responsible for several deadly outbreaks and epidemics during the last decade. Not only governments but also the scientific community reacted promptly to the outbreak, and information is shared quickly. For example, the genetic fingerprint was shared, and the 3D structure of key proteins was rapidly solved, which can be used for the discovery of potential treatments. An overview is given on the current knowledge of the spread, disease course, and molecular biology of SARS-CoV-2. We discuss potential treatment developments in the context of recent outbreaks, drug repurposing, and development timelines.

Keywords: SARS-CoV-2; antiviral; drug repurposing; protease; target.

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Figures

None
Graphical abstract
Figure 1
Figure 1
Scheme of SARS-CoV-2 and Some of Its Molecular Protein Targets
Figure 2
Figure 2
3D Structure of SARS-CoV-2 3CLpro Bound to a Covalent Peptidomimetic Inhibitor (PDB: 6LU7) The active-site Cys145 is indicated as yellow surface.
Scheme 1
Scheme 1
Selected Classes of 3CLpro Inhibitors Warheads interacting covalently with the active-site Cys145 are indicated in red.
Figure 3
Figure 3
Non-covalent Probes Binding to the Active Site of the 3CLpro Above: co-crystal structure of probe ML188 bound to SARS-CoV (PDB: 3V3M). The homology and the 3D structural similarity of SARS-CoV (green graphic) and SARS-CoV-2 (pink graphic) 3CLpro are very high. Shown is a close up view into the ML188-binding site (cyan sticks). Shown on at the bottom is synthesis and some molecular, drug metabolism and pharmacokinetic (DMPK), and pharmacology data of the probes ML188 and ML300.
Figure 4
Figure 4
Flavonoids Inhibiting 3CLPro as They Occur in Liang Quiao, the Seeds of the Forsythiae fructus Plant Used in the TCM Shuanghuanglian
Scheme 2
Scheme 2
Structures of Approved HIV Drugs (15, 16, 17, and 18) Currently Repurposed for the Treatment of COVID-19
Scheme 3
Scheme 3
Structure of Approved Drugs Inhibiting the PLpro
Figure 5
Figure 5
Structural Interaction of a Non-covalent Napthylamine Inhibitor with PLpro Co-crystal structure of HTS hit 22 (cyan sticks) with PLpro (gray sticks, PDB: 3MJ5) showing some key interaction to Tyr269 forming a hydrogen bond and a T-shaped pi stacking interaction with the naphthyl moiety 2D structures, biological activity, and half-lives of 22 and 23.
Figure 6
Figure 6
Structure of Human SARS-CoV RBD Complexed with Human ACE2 (PDB: 2AJF) as a Model for SARS-CoV-2-ACE2 Interaction ACE2 is shown in blue, the RBD of SARS is in gray, and RBM of SARS-CoV is in magenta. The closeup highlights specific hydrogen bindings of a Tyr cluster of SARS-CoV in cyan.
Figure 7
Figure 7
Structures of Four Promising Drugs for Covid-19 Treatment and an Aristeromycin Derivative Favipiravir 24 is now the first approved drug to treat Covid-19
Figure 8
Figure 8
BenevolentAI Knowledge Graph on SARS-CoV-2 and Approved Kinase Inhibitor Baricitinib 29
See this image and copyright information in PMC

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