Revisiting potential druggable targets against SARS‐CoV‐2 and repurposing therapeutics under preclinical study and clinical trials

Coronavirus disease‐19 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), is one of the most contagious diseases in human history that has already affected millions of lives worldwide. To date, no vaccines or effective therapeutics have been discovered yet that may successfully treat COVID‐19 patients or contain the transmission of the virus. Scientific communities across the globe responded rapidly and have been working relentlessly to develop drugs and vaccines, which may require considerable time. In this uncertainty, repurposing the existing antiviral drugs could be the best strategy to speed up the discovery of effective therapeutics against SARS‐CoV‐2. Moreover, drug repurposing may leave some vital information on druggable targets that could be capitalized in target‐based drug discovery. Information on possible drug targets and the progress on therapeutic and vaccine development also needs to be updated. In this review, we revisited the druggable targets that may hold promise in the development of the anti‐SARS‐CoV‐2 agent. Progresses on the development of potential therapeutics and vaccines that are under the preclinical studies and clinical trials have been highlighted. We anticipate that this review will provide valuable information that would help to accelerate the development of therapeutics and vaccines against SARS‐CoV‐2 infection.

As COVID‐19 spreads rapidly, the shortest and fastest approaches such as drug repurposing could be of the right choice that needs to be employed to discover potential therapeutics. Currently, some repurposed drugs have shown therapeutic promise, and thus Favipiravir, for instance, has already received temporary approval for use in COVID‐19 patients. Other compounds with antiviral potential, for example, β‐d‐N4‐hydroxycytidine showing inhibitory effects against Chikungunya Virus, also need to be evaluated against SARS‐CoV‐2. However, recent hype on hydroxychloroquine or chloroquine, for example, as COVID‐19 therapy should be handled carefully, as some studies claimed unprecedented side‐effects posed by these anti‐malarial drugs (Mehra et al., 2020). Simultaneously, the path to vaccine development also needs to be minimized for long‐term protection, of course addressing all the possible side‐effects. As viruses are prone to frequent mutation, vaccines based on a single target might not work for a longer time. Recently, in silico studies identified several protein subunits as vaccine candidates, combining them into a single vaccine or multiple epitope vaccines might give better results against SARS‐CoV‐2.

In this review, we revisited the current knowledge on the potential drug targets of therapeutic promise against SARS‐CoV‐2 infection and highlighted the application of the drug repurposing approach. The possible therapeutic options that are currently under clinical and preclinical studies have been discussed. We also compiled the current clinical trials mostly based on repurposing the therapeutic agents formerly designed for other indications that have been rapidly started during the early phase of the pandemic and are currently undergoing. Although far from practical application, significant progress has been made in vaccine development. Overall, this current effort leaves some valuable information on prospective druggable targets and current options of possible therapeutic as well as preventive strategies, providing a comprehensive and systematic guideline for those who are dedicated to COVID‐19 research.

Beyond the approaches that have been addressed in this review, the strategies aimed at priming the host immune responses are of great potential as individuals with a compromised immune system are particularly vulnerable to COVID‐19. Moreover, along with viral‐specific therapeutics, immunomodulatory and anti‐inflammatory agents acting against nonspecific inflammatory responses also need to be focused. The lessons learned from this emerging pandemic can help us prepare in advance for any possible future epidemics. As we live in the era of big data, systematic and multidisciplinary approaches need to be employed to find drug targets and repurposing drugs for instant drug discovery.

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Nancy Ella
Editor Board
Drug Designing: Open Access
drugdesign@eclinicalsci.org