Targeting SARS-CoV-2 main protease (M^pro) 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.

Keywords

SARS-CoV-2 / Main protease (M^pro) / ACE-2 / Carotenoids & polyphenols / Solanum lycopersicum L. / Covid-19 / Hypertension

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