Existing drugs may help with COVID-19 treatment

Computational screening of SARS-CoV-2 genomes identified several proteins which could be targeted by existing drugs to treat COVID-19

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Existing drugs designed to tackle viral infections could be repurposed to target the SARS-CoV-2 virus, cutting down the time and cost to develop a therapy. Now, an international team that included  Pooi Ling Mok of Jouf University in Saudi Arabia, and Suresh Kumar Subbiah at Bharath University in India, has used computational drug screening techniques to identify commercially available drugs that might prove effective against the strains of SARS-CoV-2 circulating in Saudi Arabia. 

“Drug studies require costly and lengthy endeavours before new compounds can be used,” wrote the authors in their paper in the Saudi Journal of Biological Sciences. “[Computational drug discovery] utilizes bioinformatics processes and data mining on huge datasets to identify new drug targets and screen existing drugs for pharmaceutical research.”

Antiviral drugs often target essential proteins that are involved in viral replication. Despite the multiplicity of mutations in SARS-CoV-2 across the world, the key viral proteins – such as the viral replication proteins 3CLPRO and PLPRO – remain highly conserved across strains. Drugs developed to inhibit these in other viruses may therefore be effective against SARS-CoV-2. 

The researchers screened 164 genomic sequences isolated from COVID-19 patients in Saudi Arabia. The isolates all had similar genomes with highly conserved proteins and elements from the original strain that first appeared in 2019. Base on this initial screening, they identified 73 similar viral therapeutic targets and matched these with existing approved drugs using the ZINC database. The team then used a multiple sequence alignment approach to identify 29 viral orthologs (viral genes conserved from common ancestors) and matched them with high-affinity drug options.  

“The main challenge was to narrow down the search for drug candidates,” says Mok. “We used multiple sequence alignment to identify closely related drug target sequences from other pathogens like SARS-CoV-1 and MERS-CoV. From there, we determined whether these candidates were possibly effective against SARS-CoV-2.”

The team found that a SARS-CoV-1 protein, the replicase polyprotein 1a (REP), is very similar to a replication protein in the SARS-CoV-2 Saudi isolates. A group of drugs based on tanshinones – bioactive compounds found in the dried root of Salvia miltiorrhiza, a plant used in traditional Chinese medicine – have strong binding affinity to REP and can inhibit the protein’s activity. Drugs containing tanshinones and their derivatives have already shown promise in clinical trials for other diseases and may prove potent against SARS-CoV-2.  

“We hope to begin testing tanshinones in the laboratory to determine their effectiveness against SARS-CoV-2 infections,” says Subbiah. Thereafter, the team members hope to combine their findings with their main research interests in stem cell treatments. “Drugs and stem cells are expected to complement each other in reducing severity in patients suffering from COVID-19.”

References

  1. Mok, P.L., et al. Computational drug screening against the SARS-CoV-2 Saudi Arabia isolates through a multiple-sequence alignment approach. Saudi Journal of Biological Sciences 28 (2502-2509) (2021)  | article

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