SARS-CoV M^pro inhibitory activity of aromatic disulfide compounds: QSAR model

Abstract

The main protease (M^pro) of SARS-associated coronavirus (SARS-CoV) had caused a high rate of mortality in 2003. Current events (2019–2020) substantiate important challenges for society due to coronaviruses. Consequently, advancing models for the antiviral activity of therapeutic agents is a necessary component of the fast development of treatment for the virus. An analogy between anti-SARS agents suggested in 2017 and anti-coronavirus COVID-19 agents are quite probable. Quantitative structure-activity relationships for SARS-CoV are developed and proposed in this study. The statistical quality of these models is quite good. Mechanistic interpretation of developed models is based on the statistical and probability quality of molecular alerts extracted from SMILES. The novel, designed structures of molecules able to possess anti-SARS activities are suggested. For the final assessment of the designed molecules inhibitory potential, developed from the obtained QSAR model, molecular docking studies were applied. Results obtained from molecular docking studies were in a good correlation with the results obtained from QSAR modeling.

Graphical Abstract

Communicated by Ramaswamy H. Sarma

Keywords:

• Coronavirus
• Severe Acute Respiratory Syndrome
• anti-SARS agents
• Monte Carlo method
• index of ideality of correlation
• molecular docking

Disclosure statement

The authors confirm they have no conflict of interest.

Additional information

Funding

A.A.T and A.P.T. are grateful for the contribution of the project LIFE-VERMEER contract (LIFE16 ENV/IT/000167) for the support. A.M.V. would like to thank the Ministry of Education and Science, the Republic of Serbia, under Project Number 172044. J.L. and DL would like to thank the NSF-CREST program for the support (grant HRD #154774).