TAT-peptide conjugated repurposing drug against SARS-CoV-2 main protease (3CLpro): Potential therapeutic intervention to combat COVID-19

Abstract

The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that originated in Chinese city of Wuhan has caused around 906,092 deaths and 28,040,853 confirmed cases worldwide (WHO, 11 September, 2020). In a life-threatening situation, where there is no specific and licensed anti-COVID-19 vaccine or medicine available; the repurposed drug might act as a silver bullet. Currently, more than 211 vaccines, 80 antibodies, 31 antiviral drugs, 35 cell-based, 6 RNA-based and 131 other drugs are in clinical trials. It is therefore utter need of the hour to develop an effective drug that can be used for the treatment of COVID-19 before a vaccine can be developed. One of the best-characterized and attractive drug targets among coronaviruses is the main protease (3CL pro ). Therefore, the current study focuses on the molecular docking analysis of TAT-peptide 47–57 (GRKKRRQRRRP)-conjugated repurposed drugs (i.e., lopinavir, ritonavir, favipiravir, and hydroxychloroquine) with SARS-CoV-2 main protease (3CL pro ) to discover potential efficacy of TAT-peptide (TP) - conjugated repurposing drugs against SARS-CoV-2. The molecular docking results validated that TP-conjugated ritonavir, lopinavir, favipiravir, and hydroxychloroquine have superior and significantly enhanced interactions with the target SARS-CoV-2 main protease. In-silico approach employed in this study suggests that the combination of the drug with TP is an excelling alternative to develop a novel drug for the treatment of SARS-CoV-2 infected patients. The development of TP based delivery of repurposing drugs might be an excellent approach to enhance the efficacy of the existing drugs for the treatment of COVID-19. The predictions from the results obtained provide invaluable information that can be utilized for the choice of candidate drugs for in vitro, in vivo and clinical trials. The outcome from this work prove crucial for exploring and developing novel cost-effective and biocompatible TP conjugated anti-SARS-CoV-2 therapeutic agents in immediate future.

Manipulated bio antimicrobial peptides from probiotic bacteria as proposed drugs for COVID-19 disease

“…Another study has also found that α-helical peptides block ACE2, leading to the inhibition of SARS-CoV-2 [ 35 ]. In another in-silico study, the efficacies of lopinavir, ritonavir, hydroxychloroquine, and favipiravir drugs were improved by adding TAT-peptide to them, and their interactions with 3CL have considerably increased [ 36 ].…”

Antimicrobial and Amyloidogenic Activity of Peptides. Can Antimicrobial Peptides Be Used against SARS-CoV-2?

“…Currently, significant resources of the scientific community are involved in the search for effective methods of treating coronavirus infection. Many strategies have been proposed, among which peptides play an important role [ 17 ]. Interestingly, a similar target effect is a characteristic of AMPs with lectin-like functions (e.g., defensins [ 18 ] and hevein-like peptides [ 19 ], which can bind to N-glycosylated sites of the viral spike protein or the receptor, which ultimately prevents penetration of the virus into the host cell [ 20 , 21 ].…”

Natural Products and Nutrients against Different Viral Diseases: Prospects in Prevention and Treatment of SARS-CoV-2

“…This review is based on the treatments given in the case of SARS-CoV and MERS, which could also be effective against SARS-CoV-2 since SARS-CoV-2 is closely related to SARS-CoV and have 80% sequence identical [ 8 ]. Plants are a good source of natural medication and an alternative to antibiotic treatment because the excessive use of antibiotics is responsible for drug resistance.…”

“…SARS-CoV-2 genome is 80% similar to the previous human coronavirus SARS-CoV [ 8 ]. For some of the encoded proteins such as coronavirus main proteinase (3CLpro), papain-like protease (PLpro), and RNA-dependent RNA polymerase (RdRp) the sequence similarity is very high (96%) between SARS-CoV, and SARS-CoV-2 [ 9 ].…”