Eravacycline for COVID-19

AbstractDrug repurposing, also known as drug repositioning, is a currently tested approach by which new uses are being assigned for already tested drugs. In this case there are antibiotics that are used to combat bacterial infections. However, antibiotics are among the drugs that have been studied for possible antiviral activities. Therefore, the aim of this work is to carry out a review of the studies of antibiotics that could be repositioned for the treatment of viral infections. Among the main antibiotics that have demonstrated antiviral activity are macrolides and glycopeptides. In addition, several antibiotics from the group of tetracyclines, fluoroquinolones, cephalosporins and aminoglycosides have also been studied for their antiviral activity. These antibiotics have demonstrated antiviral activity against both RNA and DNA viruses, including the recent pandemic virus SARS-CoV-2. Some of these antibiotics were selected in addition to its antiviral activity for their immunomodulatory and anti-inflammatory properties. Of the antibiotics that present antiviral activity, in many cases the mechanisms of action are not exactly known. The use of these antibiotics to combat viral infections remains controversial and is not generally accepted, since clinical trials are required to prove its effectiveness. Therefore, there is currently no antibiotic approved as antiviral therapy. Hence is necessary to present the studies carried out on antibiotics that can be repositioned in the future as antiviral drugs.

AbstractTo attain promising pharmacotherapies, researchers have applied drug repurposing (DR) techniques to discover the candidate medicines to combat the coronavirus disease 2019 (COVID-19) outbreak. Although many DR approaches have been introduced for treating different diseases, only structure-based DR (SBDR) methods can be employed as the first therapeutic option against the COVID-19 pandemic because they rely on the rudimentary information about the diseases such as the sequence of the severe acute respiratory syndrome coronavirus 2 genome. Hence, to try out new treatments for the disease, the first attempts have been made based on the SBDR methods which seem to be among the proper choices for discovering the potential medications against the emerging and re-emerging infectious diseases. Given the importance of SBDR approaches, in the present review, well-known SBDR methods are summarized, and their merits are investigated. Then, the databases and software applications, utilized for repurposing the drugs against COVID-19, are introduced. Besides, the identified drugs are categorized based on their targets. Finally, a comparison is made between the SBDR approaches and other DR methods, and some possible future directions are proposed.

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.

Abstract Using as a template the crystal structure of the SARS-CoV-2 main protease, we developed a pharmacophore model of functional centers of the protease inhibitor-binding pocket. With this model, we conducted data mining of the conformational database of FDA-approved drugs. This search brought 64 compounds that can be potential inhibitors of the SARS-CoV-2 protease. The conformations of these compounds undergone 3D fingerprint similarity clusterization. Then we conducted docking of possible conformers of these drugs to the binding pocket of the protease. We also conducted the same docking of random compounds. Free energies of the docking interaction for the selected compounds were clearly lower than random compounds. Three of the selected compounds were carfilzomib, cyclosporine A, and azithromycin—the drugs that already are tested for COVID-19 treatment. Among the selected compounds are two HIV protease inhibitors and two hepatitis C protease inhibitors. We recommend testing of the selected compounds for treatment of COVID-19.