Targeting SARS-CoV-2 main protease (Mpro) and human ACE-2: A virtual screening of carotenoids and polyphenols from tomato (Solanum lycopersicum L.) to combat Covid-19

Abstract

Background

Human angiotensin-converting enzyme-2 (ACE-2) and severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) main protease (M^pro) have been established as the prime targets to restrict viral invasion and replication inside the host, respectively.

Methods

The current study delineated the SARS-CoV-2 M^pro as well as human ACE-2 inhibitory potential of carotenoids and polyphenols from tomato (Solanum lycopersicum L.) via in-silico interaction studies.

Results

Our drug-likeness studies showed that the selected carotenoids and polyphenols exhibited acceptable Lipinski’s score and ADME determinants. Further, in-silico molecular modelling studies revealed that β-carotene, among other carotenoids, topped the binding score (ΔG: −6.75 ​kcal/mol; Ki: 11.32 ​μM) against SARS-CoV-2 M^pro, whereas, cyanidin was the best inhibitor of SARS-CoV-2 M^pro (−7.24 ​kcal/mol; Ki: 4.92 ​μM) amongst polyphenols. Similarly, α-carotene from carotenoids exhibited strongest human ACE-2 inhibitory activity (ΔG: −8.85 ​kcal/mol; Ki: 326.13 ​μM), whereas, cyanidin from polyphenols showed best binding affinity against human ACE-2 (ΔG: −7.24 ​kcal/mol; Ki: 4.89 ​μM). In contrast, 6-(ethylamino)-pyridine-3-carbonitrile, standard inhibitor of SARS-CoV-2 M^pro, exhibited comparatively weaker binding (ΔG: −4.78 ​kcal/mol; Ki: 267.49 ​μM), whereas, telmisartan (reference ACE-2 inhibitor) also exhibited lesser affinity (ΔG: −6.40 ​kcal/mol; Ki: 20.40 ​μM). Further exploration via MDS studies also validated the dynamic behavior and stability of protein-ligand complexes as evident by desirable RMSD, RMSF, Rg, and SASA.

Conclusion

The current study established carotenoids and polyphenols from S. lycopersicum L. as finer substitutes of reference standards against SARS-CoV-2 M^pro and human ACE-2 activity in combating SARS-CoV-2 infection.