In silico molecular docking analysis for repurposing therapeutics against multiple proteins from SARS-CoV-2

Abstract

SARS-CoV-2 has devastated the world with its rapid spread and fatality. The researchers across the globe are struggling hard to search a drug to treat this infection. Understanding the time constraint, the best approach is to study clinically approved drugs for control of this deadly pandemic of COVID 19. The repurposing of such drugs can be supported with the study of molecular interactions to enhance the possibility of application. The present work is a molecular docking study of proteins responsible for viral propagation namely 3Clpro, Nsp10/16, Spike protein, SARS protein receptor binding domain, Nsp 9 viral single strand binding protein and viral helicase. The protein through virus enters the host cell-human angiotensin-converting enzyme 2 (ACE2) receptor, is also used as a target for molecular docking. The docking was done with most discussed drugs for SARS-CoV-2 like Ritonavir, Lopinavir, Remdesivir, Chloroquine, Hydroxychloroquine (HCQ), routine antiviral drugs like Oseltamivir and Ribavirin. In addition, small molecules with anti-inflammatory actions like Mycophenolic acid (MPA), Pemirolast, Isoniazid and Eriodictyol were also tested. The generated data confirms the potential of Ritonavir, Lopinavir and Remdesivir as a therapeutic candidate against SARS-CoV-2. It is observed that Eriodictyol binds to almost all selected target proteins with good binding energy, suggesting its importance in treatment of COVID 19. Molecular interactions of Ritonavir, Lopinavir and Remdesivir against SARS-CoV-2 proteins enhanced their potential as a candidate drug for treatment of COVID-19. Eriodictyol had emerged as a new repurposing drug that can be used in COVID-19.

Pharmacological Activity of Eriodictyol: The Major Natural Polyphenolic Flavanone

“…Recently, an in silico molecular docking study reported that ER has good binding energies and antiviral effects by its cellular multi-target ability against multiple proteins from SARS-CoV-2, especially the angiotensin converting enzyme 2 (ACE2) [ 95 ]. Moreover, compared to many already known drugs, ER strongly binds to virus replicating proteins such as SARS-CoV-2 helicase which potentially helps recognize RNA: DNA duplex is a unique feature of viruses, and active sites of SARS-CoV-2 spike glycoprotein C chain having 10 amino acids [ 95 ]. Hence, ER appeared to be a novel multi-target molecule for repurposing against SARS-CoV-2.…”

Exploring the new potential antiviral constituents of Moringa oliefera for SARS-COV-2 pathogenesis: An in silico molecular docking and dynamic studies

“…In a study, two anti-inflammatory drugs, pemirolast and eriodictyol were docked against nsp9 with the resulting binding energy of −6.5 kcal/mol and further suggest their role in inhibiting infection. It has been further reported that retonavir and remdesivir are potential drugs against nsp10, suggesting their ability to inhibit viral transcription [11] . Thus, both proteins can be proved as a potential therapeutic target in combating SARS-CoV-2 pathogenesis.…”

Testing of the inhibitory effects of loratadine and desloratadine on SARS-CoV-2 spike pseudotyped virus viropexis

“…However, developing a new, effective, and safe vaccine often requires years and poses great risks [ 16 ]. At the same time, a lot of compounds obtained from natural products have been reported for their potential activity in preventing viral entry into cells using in silico analysis and in vitro inhibition experiments [ 17 , 18 ]. For example, curcumin has been reported to modulate the events of SARS-CoV-2 cellular entry and replication [ 19 ].…”