Title

Anti-COVID-19 activity of some benzofused 1,2,3-triazolesulfonamide hybrids using in silico and in vitro analyses

Document Type

Article

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a pandemic fatal infection with no known treatment. The severity of the disease and the fast viral mutations forced the scientific community to search for potential solution. Here in the present manuscript, some benzofused1,2,3triazolesulfonamide hybrids were synthesized and evaluated for their anti- SARS-CoV-2 activity using in silico prediction then the most potent compounds were assessed using in-Vitro analysis. The in-Silico study was assessed against RNA dependent RNA polymerase, Spike protein S1, Main protease (3CLpro) and 2′-O-methyltransferase (nsp16). It was found that 4b and 4c showed high binding scores against RNA dependent RNA polymerase reached −8.40 and −8.75 ​kcal/mol, respectively compared to the approved antiviral (remdesivir −6.77 ​kcal/mol). Upon testing the binding score with SARS-CoV-2 Spike protein it was revealed that 4c exhibited the highest score (−7.22 ​kcal/mol) compared to the reference antibacterial drug Ceftazidime (−6.36 ​kcal/mol). Surprisingly, the two compounds 4b and 4c showed the highest binding scores against SARS-CoV-2 3CLpro (−8.75, −8.48 ​kcal/mol, respectively) and nsp16 (- 8.84 and – 8.89 ​kcal/mol, respectively) displaying many types of interaction with all the enzymes binding sites. The derivatives 4b and 4c were examined in vitro for their potential anti-SARS-CoV-2 and it was revealed that 4c was the most promising compound with IC50 reached 758.8108 ​mM and complete (100%) inhibition of the binding of SARS-CoV-2 virus to human ACE2 can be accomplished by using 0.01 ​mg.

Publication Date

10-15-2021

Faculty

Faculty of Applied Health Sciences Technology

Subject Area

Physical Sciences, General Chemical Engineering, General Computer Science, General Chemistry

Indexed in Scopus

yes

Indexed in Web Of Science

yes

DOI

https://doi.org/10.1016/j.chemolab.2021.104421

Volume

217

Keywords

Anti-COVID-19, Docking study, In vitro, Lopinavir, N3, Remdesivir, Sinefungin

ISSN

01697439

eISSN

18733239

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