Dolutegravir for COVID-19

The emergence of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected many countries throughout the world. As urgency is a necessity, most efforts have focused on identifying small molecule drugs that can be repurposed for use as anti-SARS-CoV-2 agents. Although several drug candidates have been identified using in silico method and in vitro studies, most of these drugs require the support of in vivo data before they can be considered for clinical trials. Several drugs are considered promising therapeutic agents for COVID-19. In addition to the direct-acting antiviral drugs, supportive therapies including traditional Chinese medicine, immunotherapies, immunomodulators, and nutritional therapy could contribute a major role in treating COVID-19 patients. Some of these drugs have already been included in the treatment guidelines, recommendations, and standard operating procedures. In this article, we comprehensively review the approved and potential therapeutic drugs, immune cells-based therapies, immunomodulatory agents/drugs, herbs and plant metabolites, nutritional and dietary for COVID-19.

The rapidly enlarging COVID-19 pandemic caused by novel SARS-coronavirus 2 is a globalpublic health emergency of unprecedented level. Therefore the need of a drug or vaccine thatcounter SARS-CoV-2 is an utmost requirement at this time. Upon infection the ssRNA genomeof SARS-CoV-2 is translated into large polyprotein which further processed into differentnonstructural proteins to form viral replication complex by virtue of virus specific proteases:main protease (3-CL protease) and papain protease. This indispensable function of main proteasein virus replication makes this enzyme a promising target for the development of inhibitors andpotential treatment therapy for novel coronavirus infection. The recently concluded α-ketoamideligand bound X-ray crystal structure of SARS-CoV-2 Mpro (PDB ID: 6Y2F) from Zhang et al.has revealed the potential inhibitor binding mechanism and the determinants responsible forinvolved molecular interactions. Here, we have carried out a virtual screening and moleculardocking study of FDA approved drugs primarily targeted for other viral infections, to investigatetheir binding affinity in Mpro active site. Virtual screening has identified a number of antiviraldrugs, top ten of which on the basis of their bending energy score are further examined through molecular docking with Mpro. Docking studies revealed that drug Lopinavir-Ritonavir, Tipranavirand Raltegravir among others binds in the active site of the protease with similar or higheraffinity than the crystal bound inhibitor α-ketoamide. However, the in-vitro efficacies of the drugmolecules tested in this study, further needs to be corroborated by carrying out biochemical andstructural investigation. Moreover, this study advances the potential use of existing drugs to beinvestigated and used to contain the rapidly expanding SARS-CoV-2 infection.

SummaryA novel coronavirus, named SARS-CoV-2, emerged in 2019 from Hubei region in China and rapidly spread worldwide. As no approved therapeutics exists to treat Covid-19, the disease associated to SARS-Cov-2, there is an urgent need to propose molecules that could quickly enter into clinics. Repurposing of approved drugs is a strategy that can bypass the time consuming stages of drug development. In this study, we screened the Prestwick Chemical Library® composed of 1,520 approved drugs in an infected cell-based assay. 90 compounds were identified. The robustness of the screen was assessed by the identification of drugs, such as Chloroquine derivatives and protease inhibitors, already in clinical trials. The hits were sorted according to their chemical composition and their known therapeutic effect, then EC50 and CC50 were determined for a subset of compounds. Several drugs, such as Azithromycine, Opipramol, Quinidine or Omeprazol present antiviral potency with 2<EC50<20µM. By providing new information on molecules inhibiting SARS-CoV-2 replication in vitro, this study could contribute to the short-term repurposing of drugs against Covid-19.

AbstractA novel coronavirus, named SARS-CoV-2, emerged in 2019 in China and rapidly spread worldwide. As no approved therapeutics exists to treat COVID-19, the disease associated to SARS-Cov-2, there is an urgent need to propose molecules that could quickly enter into clinics. Repurposing of approved drugs is a strategy that can bypass the time-consuming stages of drug development. In this study, we screened the PRESTWICK CHEMICAL LIBRARY composed of 1,520 approved drugs in an infected cell-based assay. The robustness of the screen was assessed by the identification of drugs that already demonstrated in vitro antiviral effect against SARS-CoV-2. Thereby, 90 compounds were identified as positive hits from the screen and were grouped according to their chemical composition and their known therapeutic effect. Then EC50 and CC50 were determined for a subset of 15 compounds from a panel of 23 selected drugs covering the different groups. Eleven compounds such as macrolides antibiotics, proton pump inhibitors, antiarrhythmic agents or CNS drugs emerged showing antiviral potency with 2 < EC50 ≤ 20 µM. By providing new information on molecules inhibiting SARS-CoV-2 replication in vitro, this study provides information for the selection of drugs to be further validated in vivo. Disclaimer: This study corresponds to the early stages of antiviral development and the results do not support by themselves the use of the selected drugs to treat SARS-CoV-2 infection.