Your browser doesn't support javascript.
Aminoglycosides as potential inhibitors of SARS-CoV-2 main protease: an in silico drug repurposing study on FDA-approved antiviral and anti-infection agents.
Ahmed, Mohammad Z; Zia, Qamar; Haque, Anzarul; Alqahtani, Ali S; Almarfadi, Omar M; Banawas, Saeed; Alqahtani, Mohammed S; Ameta, Keshav L; Haque, Shafiul.
  • Ahmed MZ; Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. Electronic address: mahmed4@ksu.edu.sa.
  • Zia Q; Health and Basic Science Research Centre, Majmaah University, Majmaah 11952, Saudi Arabia; Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Majmaah 11952, Saudi Arabia.
  • Haque A; Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin AbdulAziz University, Al Kharj 11942, Saudi Arabia.
  • Alqahtani AS; Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
  • Almarfadi OM; Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
  • Banawas S; Health and Basic Science Research Centre, Majmaah University, Majmaah 11952, Saudi Arabia; Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Majmaah 11952, Saudi Arabia.
  • Alqahtani MS; Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
  • Ameta KL; Department of Chemistry, School of Liberal Arts and Sciences, Mody University of Science and Technology, Lakshmangarh, Rajasthan 332311, India.
  • Haque S; Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan 45142, Saudi Arabia.
J Infect Public Health ; 14(5): 611-619, 2021 May.
Article in English | MEDLINE | ID: covidwho-1188793
ABSTRACT

BACKGROUND:

The emergence and spread of SARS-CoV-2 throughout the world has created an enormous socioeconomic impact. Although there are several promising drug candidates in clinical trials, none is available clinically. Thus, the drug repurposing approach may help to overcome the current pandemic.

METHODS:

The main protease (Mpro) of SARS-CoV-2 is crucial for cleaving nascent polypeptide chains. Here, FDA-approved antiviral and anti-infection drugs were screened by high-throughput virtual screening (HTVS) followed by re-docking with standard-precision (SP) and extra-precision (XP) molecular docking. The most potent drug's binding was further validated by free energy calculations (Prime/MM-GBSA) and molecular dynamics (MD) simulation.

RESULTS:

Out of 1397 potential drugs, 157 showed considerable affinity toward Mpro. After HTVS, SP, and XP molecular docking, four high-affinity lead drugs (Iodixanol, Amikacin, Troxerutin, and Rutin) with docking energies -10.629 to -11.776kcal/mol range were identified. Among them, Amikacin exhibited the lowest Prime/MM-GBSA energy (-73.800kcal/mol). It led us to evaluate other aminoglycosides (Neomycin, Paramomycin, Gentamycin, Streptomycin, and Tobramycin) against Mpro. All aminoglycosides were bound to the substrate-binding site of Mpro and interacted with crucial residues. Altogether, Amikacin was found to be the most potent inhibitor of Mpro. MD simulations of the Amikacin-Mpro complex suggested the formation of a complex stabilized by hydrogen bonds, salt bridges, and van der Waals interactions.

CONCLUSION:

Aminoglycosides may serve as a scaffold to design potent drug molecules against COVID-19. However, further validation by in vitro and in vivo studies is required before using aminoglycosides as an anti-COVID-19 agent.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Drug Repositioning / COVID-19 Type of study: Experimental Studies / Prognostic study Limits: Humans Language: English Journal: J Infect Public Health Journal subject: Communicable Diseases / Public Health Year: 2021 Document Type: Article

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: Drug Repositioning / COVID-19 Type of study: Experimental Studies / Prognostic study Limits: Humans Language: English Journal: J Infect Public Health Journal subject: Communicable Diseases / Public Health Year: 2021 Document Type: Article