Therapeutic development by repurposing drugs targeting SARS-CoV-2 spike protein interactions by simulation studies

Qazi Mohammad Sajid Jamal; Varish Ahmad; Ali H Alharbi; Mohammad Azam Ansari; Mohammad A Alzohairy; Ahmad Almatroudi; Saad Alghamdi; Mohammad N Alomary; Sami AlYahya; Nashwa Talaat Shesha; Suriya Rehman

doi:10.1016/j.sjbs.2021.04.057

Therapeutic development by repurposing drugs targeting SARS-CoV-2 spike protein interactions by simulation studies

Saudi J Biol Sci. 2021 Aug;28(8):4560-4568. doi: 10.1016/j.sjbs.2021.04.057. Epub 2021 Apr 28.

Affiliations

¹ Department of Health Informatics, College of Public Health and Health Informatics, Qassim University, Al Bukayriyah, Saudi Arabia.
² Health Information Technology Department, Faculty of Applied Studies, King Abdulaziz University, Jeddah, Saudi Arabia.
³ Department of Epidemic Disease Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia.
⁴ Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Qassim 51431, Saudi Arabia.
⁵ Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia.
⁶ National Centre for Biotechnology, King Abdulaziz City for Science and Technology (KACST), P.O. Box 6086, Riyadh 11442, Saudi Arabia.
⁷ Regional Laboratory, Directorate of Health Affairs Makkah, Saudi Arabia.

Abstract

The human-to-human transmitted respiratory illness in COVID-19 affected by the pathogenic Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2), which appeared in the last of December 2019 in Wuhan, China, and rapidly spread in many countries. Thereon, based on the urgent need for therapeutic molecules, we conducted in silico based docking and simulation molecular interaction studies on repurposing drugs, targeting SARS-CoV-2 spike protein. Further, the best binding energy of doxorubicin interacting with virus spike protein (PDB: 6VYB) was observed to be -6.38 kcal/mol and it was followed by exemestane and gatifloxacin. The molecular simulation dynamics analysis of doxorubicin, Reference Mean Square Deviation (RMSD), Root Mean Square fluctuation (RMSF), Radius of Gyration (Rg), and formation of hydrogen bonds plot interpretation suggested, a significant deviation and fluctuation of Doxorubicin-Spike RBD complex during the whole simulation period. The Rg analysis has stated that the Doxorubicin-Spike RBD complex was stable during 15,000-35,000 ps MDS. The results have suggested that doxorubicin could inhibit the virus spike protein and prevent the access of the SARS-CoV-2 to the host cell. Thus, in-vitro/in-vivo research on these drugs could be advantageous to evaluate significant molecules that control the COVID-19 disease.

Keywords: Antiviral drugs; Doxorubicin; Exemestane; Gatifloxacin; Hbond, Hydrogen bond; Pandemic; SARS-CoV-2; Spike protein; kcal/mol, Kilocalories per mole; nm, nanometer; ns, nanosecond; ps, picosecond; uM, Micro Molar; Å, Angstrom.