Stalling SARS-CoV2 infection with stem cells: can regenerating perinatal tissue mesenchymal stem cells offer a multi-tiered therapeutic approach to COVID-19?

The emergence of COVID-19 has created a major health crisis across the globe. Invasion of SARS-CoV-2 into the lungs causes acute respiratory distress syndrome (ARDS) that result in the damage of lung alveolar epithelial cells. Currently, there is no standard treatment available to treat the disease and the resultant lung scarring is irreversible even after recovery. This has prompted researchers across the globe to focus on developing new therapeutics and vaccines for the treatment and prevention of COVID-19. Mesenchymal stem cells (MSCs) have emerged as an efficient drug screening platform and MSC-derived organoids has found applications in disease modeling and drug discovery. Perinatal tissue derived MSC based cell therapies have been explored in the treatment of various disease conditions including ARDS because of their enhanced regenerative and immunomodulatory properties. The multi-utility properties of MSCs have been described in this review wherein we discuss the potential use of MSC-derived lung organoids in screening of novel therapeutic compounds for COVID-19 and also in disease modeling to better understand the pathogenesis of the disease. This article also summarizes the rationale behind the development of MSC-based cell- and cell-free therapies and vaccines for COVID-19 with a focus on the current progress in this area. With the pandemic raging, an important necessity is to develop novel treatment strategies which will not only alleviate the disease symptoms but also avoid any off-target effects which could further increase post infection sequelae. Naturally occurring mesenchymal stem cells could be the magic bullet which fulfil these criteria.

Computational screening of dual inhibitors from FDA approved antiviral drugs on SARS-CoV-2 spike protein and the main protease using molecular docking approach.

The deadly disease-causing novel coronavirus has recently swept across the world and endangered many human lives. Although, various research on therapeutic measures to solve this pandemic crisis has been published; no favourable results have been achieved. We propose the use of potential FDA-approved dual inhibitors which can inhibit two targets (either on entry-level or the main protease) for the effective treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We screened 12 FDA-approved antiviral inhibitors listed in Drug bank and analysed the ADMET properties of each drug of interest to study the bioavailability, safety and toxicity. Two potential targets, the spike protein and the main protease of SARS-CoV-2 obtained from PDB have been used for molecular docking. All the selected drugs were docked with both targets and demonstrated strong hydrogen bond (HB) interactions in multiple active sites. Amongst these, the range of binding energy was from 3-7 kcal/mol for spike protein and 2-8 kcal/mol for the main protease. Upon comparison of all the processed drugs ganciclovir and zanamivir displayed significant binding energy with HB interactions with both, spike (-9.2 and -9 kcal/mol respectively) and the main protease (-9 kcal/mol). Ribavirin and tenofovir showed significant binding energy above -8 kcal/mol with seven HB interactions with the main protease and also spike protein. The novel findings regarding the antiviral properties of these dual inhibitors using a computational approach will be a good starting point for the efficacy determination of these drugs for pre-clinical and clinical studies aimed at developing active antivirals to target SARS-CoV-2. Keywords: SARS-CoV-2; FDA-approved drugs; viral inhibitors; in-silico analysis; molecular docking.

Comprehensive review on the prevailing COVID-19 therapeutics and the potential of repurposing SARS-CoV-1 candidate drugs to target SARS-CoV-2 as a fast-track treatment and prevention option.

The recent seemingly uncontrollable pandemic caused by the novel severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has been able to spread quickly due to the non-availability of effective antivirals or vaccines. The virus has structural and non-structural proteins that are considered as possible targets. Receptor recognition is the critical determinant and preliminary phase of viral infection to enter the host cell and causes tissue tropism. We have conducted a comprehensive review of relevant publication on in vitro, in silico, in vivo and clinical evaluation of drug candidates ranging from broad-spectrum antivirals to natural molecules targeted towards viral spike protein in addition to evaluate their suitability as therapies based on an analysis of the similarities between SARS-CoV-1 and SARS-CoV-2. In general, antiviral targets are based on two strategies, either targeting the host or the host's immune cell. We have reviewed the available details on the SARS-CoV-2 strain's host-viral binding sites entry mechanism, alongside recently tested effective antivirals. The hypothesis of this review may provide clear insight for researchers and physicians who are struggling to narrow down scientific options to control the current pandemic. Overall, we found that the promising efficacious drug candidates reported against SARS-CoV-1 could be considered for drug repurposing; this might help to identify a potential drug for therapeutic measures and development of vaccine for COVID-19.