Potential of coronavirus 3C-like protease inhibitors for the development of new anti-SARS-CoV-2 drugs: Insights from structures of protease and inhibitors

Abstract

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A review on possible mechanistic insights of Nitazoxanide for repurposing in COVID-19

“…Inhibition of 3CLpro: The active site of 3CLpro of SARS-CoV-2 contains Cys145 and His41 residues forming a catalytic dyad, ( He et al, 2020 ; Tahir ul Qamar et al, 2020 ) where cysteine thiol (-SH) functions as a common nucleophile (electron donating group) responsible for proteolytic cleavage ( Yang et al, 2003 ). SAR studies of pyrazolones and pyrimidines revealed that the presence of aromatic nitro (-NO 2 ) enhances cysteine protease inhibition activity, where the oxygen of the NO 2 forms a H-bond with side chains of Gly143 and Cys145, while the phenyl ring forms hydrophobic interactions ( Pillaiyar et al, 2016 ).…”

Optimization and evaluation of propolis liposomes as a promising therapeutic approach for COVID-19

“…To gain more insight into the effect of both propolis extract and the propolis liposomes on the inhibition of viral RNA 3CL-protease and consequently blocking viral replication, 3CL- Protease (SARS-CoV-2) Assay Kit was used ( He et al, 2020 ). 3CL-protease inhibition was tested for propolis extract, propolis liposomes, solvent of the extract (alcohol) and Remdesivir as a positive control.…”

Molecular mechanisms of the novel coronavirus SARS-CoV-2 and potential anti-COVID19 pharmacological targets since the outbreak of the pandemic

“…Significant conservation of the catalytic site has been observed between the 3CLpro structures of the SARS-CoV, MERS-CoV, and SARS-CoV-2 viruses. This discovery allows the examination of already established inhibitors of the other coronaviruses' 3CLpro enzyme, under the possibility that they may prove effective against the 3CLpro of the novel SARS-CoV-2 ( He et al, 2020 ). Furthermore, research groups have been establishing screening processes for the possible repurposing of various drugs.…”