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Review
. 2022 Jan 5;17(1):e202100576.
doi: 10.1002/cmdc.202100576. Epub 2021 Oct 28.

A Patent Review on SARS Coronavirus Main Protease (3CLpro ) Inhibitors

C S Brian Chia  1 , Weijun Xu  1 , Pearly Shuyi Ng  1
Affiliations
Review

A Patent Review on SARS Coronavirus Main Protease (3CLpro ) Inhibitors

C S Brian Chia et al. ChemMedChem. .

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is an unprecedented global health emergency causing more than 4.2 million fatalities as of 30 July 2021. Only three antiviral therapies have been approved or granted emergency use authorization by the FDA. The SARS-CoV-2 3CL protease (3CLpro ) is deemed an attractive drug target as it plays an essential role in viral polyprotein processing and pathogenesis, although no inhibitors have been approved. This patent review discusses SARS coronavirus 3CLpro inhibitors that have been filed up to 30 July 2021, giving an overview on the types of inhibitors that have generated commercial interest, especially amongst drug companies. Insights into the common structural motifs required for active site binding is also discussed.

Keywords: 3CLpro; COVID-19; Mpro; SARS-CoV-2; cysteine protease inhibitor.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
General scaffolds from WO 2004/093860.
Figure 2
Figure 2
Structures from WO 2004/101742. (a) general scaffold; (b–f) exemplified structures.
Figure 3
Figure 3
Structures from US 2006/0014821. (a, b) general scaffolds; (c–f) exemplified structures.
Figure 4
Figure 4
Structures from WO 2005/041904. (a–e) exemplified structures with the most potent K is against SARS‐CoV 3CLpro.
Figure 5
Figure 5
Structures from WO 2005/066123. (a) general scaffold; (b–f) exemplified structures.
Figure 6
Figure 6
Structures from WO 2005/113580. (a) general scaffold; (b–f) exemplified structures.
Figure 7
Figure 7
Six most potent SARS‐CoV 3CLpro inhibitors reported in US 2006/0019967.
Figure 8
Figure 8
Structures from WO 2006/061714. (a) general scaffold; (b–e) exemplified structures.
Figure 9
Figure 9
Exemplified structure from CN 1965833 A.
Figure 10
Figure 10
Structures from WO 2006/061714. (a) general scaffold; (b–f) exemplified structures.
Figure 11
Figure 11
Structures from WO 2006/095624. (a) general scaffold; (b–f) exemplified structures.
Figure 12
Figure 12
Structures from WO 2007/075145. (a) general scaffold; (b–e) exemplified structures.
Figure 13
Figure 13
Structures from CN 103159665B. (a) general scaffold; (b–f) exemplified structures.
Figure 14
Figure 14
Structures from WO 2013/049382. (a) general scaffold; (b–f) exemplified structures.
Figure 15
Figure 15
Structure of quercetin from KR 1020130002975.
Figure 16
Figure 16
Structures from WO 2013/166319. (a, b) general scaffolds; (c–i) exemplified structures.
Figure 17
Figure 17
Structures from CN 106176728 A. (a) general scaffold; (b–f) top five most potent inhibitors.
Figure 18
Figure 18
Structures from WO 2017/114509. (a) general scaffold; (b–f) most potent exemplified inhibitors against SARS‐CoV 3CLpro.
Figure 19
Figure 19
Structures from US 2017/0313685. (a) general scaffold; (b–f) most potent exemplified structures.
Figure 20
Figure 20
Structures from WO 2017/222935. (a) general scaffold; (b–f) exemplified structures.
Figure 21
Figure 21
Structure of acamprosate calcium from CN 108785293 A.
Figure 22
Figure 22
Structures from WO 2018/042343. (a) general scaffold; (b–e) exemplified structures.
Figure 23
Figure 23
Structures from WO 2020/030143. (a) general scaffold; (b–f) most potent exemplified MERS‐CoV 3CLpro inhibitors.
Figure 24
Figure 24
Structures from WO 2021/176369. (a) peptidomimetic general scaffold; (b–i) exemplified inhibitors.
Figure 25
Figure 25
Structure of PF‐07321332.
See this image and copyright information in PMC

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