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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.

ABSTRACT: 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.

SUBMITTER: Sabarimurugan S

PROVIDER: S-EPMC7607133 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Given the scale and rapid spread of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, or 2019-nCoV), there is an urgent need to identify therapeutics that are effective against COVID-19 before vaccines are available. Since the current rate of SARS-CoV-2 knowledge acquisition via traditional research methods is not sufficient to match the rapid spread of the virus, novel strategies of drug discovery for SARS-CoV-2 infection are required. Structure-based virtual screening for example relies primarily on docking scores and does not take the importance of key residues into consideration, which may lead to a significantly higher incidence rate of false-positive results. Our novel in silico approach, which overcomes these limitations, can be utilized to quickly evaluate FDA-approved drugs for repurposing and combination, as well as designing new chemical agents with therapeutic potential for COVID-19. As a result, anti-HIV or antiviral drugs (lopinavir, tenofovir disoproxil, fosamprenavir and ganciclovir), antiflu drugs (peramivir and zanamivir) and an anti-HCV drug (sofosbuvir) are predicted to bind to 3CLPro in SARS-CoV-2 with therapeutic potential for COVID-19 infection by our new protocol. In addition, we also propose three antidiabetic drugs (acarbose, glyburide and tolazamide) for the potential treatment of COVID-19. Finally, we apply our new virus chemogenomics knowledgebase platform with the integrated machine-learning computing algorithms to identify the potential drug combinations (e.g. remdesivir+chloroquine), which are congruent with ongoing clinical trials. In addition, another 10 compounds from CAS COVID-19 antiviral candidate compounds dataset are also suggested by Molecular Complex Characterizing System with potential treatment for COVID-19. Our work provides a novel strategy for the repurposing and combinations of drugs in the market and for prediction of chemical candidates with anti-COVID-19 potential.

Project description:Severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2 is a virus that belongs to the Coronaviridae family. This group of viruses commonly causes colds but possesses a tremendous pathogenic potential. In humans, an outbreak of SARS caused by the SARS-CoV virus was first reported in 2003, followed by 2012 when the Middle East respiratory syndrome coronavirus (MERS-CoV) led to an outbreak of Middle East respiratory syndrome (MERS). Moreover, COVID-19 represents a serious socioeconomic and global health problem that has already claimed more than four million lives. To date, there are only a handful of therapeutic options to combat this disease, and only a single direct-acting antiviral, the conditionally approved remdesivir. Since there is an urgent need for active drugs against SARS-CoV-2, the strategy of drug repurposing represents one of the fastest ways to achieve this goal. An in silico drug repurposing study using two methods was conducted. A structure-based virtual screening of the FDA-approved drug database on SARS-CoV-2 main protease was performed, and the 11 highest-scoring compounds with known 3CLpro activity were identified while the methodology was used to report further 11 potential and completely novel 3CLpro inhibitors. Then, inverse molecular docking was performed on the entire viral protein database as well as on the Coronaviridae family protein subset to examine the hit compounds in detail. Instead of target fishing, inverse docking fingerprints were generated for each hit compound as well as for the five most frequently reported and direct-acting repurposed drugs that served as controls. In this way, the target-hitting space was examined and compared and we can support the further biological evaluation of all 11 newly reported hits on SARS-CoV-2 3CLpro as well as recommend further in-depth studies on antihelminthic class member compounds. The authors acknowledge the general usefulness of this approach for a full-fledged inverse docking fingerprint screening in the future.

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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.

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