Veterinary scientists explore alternative strategy for developing drugs against COVID-19

Vijay Mohan
Tribune News Service
Chandigarh, June 5

Joining the fight against COIVD-19 pandemic, veterinary scientists at the National Centre for Veterinary Type Cultures (NCVTC) are exploring alternative strategies to develop drugs against the deadly virus.

They will screen their library of 94 small molecule chemical inhibitors for anti-virals against various strains of coronaviruses.

The molecules are known to inhibit cellular kinases, phosphatases, and epigenetic regulators.

The targets of these inhibitors are well characterised in cancer, but their role in the virus life cycle is not yet known. The selected candidates with anti-coronavirus activity will be subjected to study their molecular mechanism of action, besides examining the generation of potential drug-resistant virus variants.

“Chemical library screening in medicinal chemistry research is a useful methodology that considerably shortens drug discovery and development cycle, especially for newly identified etiologic agents, such as SARS-Cov-2,” said Prof Sandeep Verma, Secretary, SERB.

“Such an approach provides rapid access to useful pharmacophores and narrows down the search for preferred molecular scaffolds and is also compatible with high-throughput robotic assays. While supporting CoV-2 vaccine development programs, it is also imperative to have sufficient focus toward anti-coronavirus drug discovery pipeline,” he added.

The study has been approved by the Science and Engineering Research Board (SERB). Based at Hisar, NCVTC functions under the Indian Council of Agricultural Research.

It is a microbial repository responsible for the conservation of microbes where microbial biodiversity of animal origin is being conserved so that it can be utilized effectively for research, teaching and development of biologicals for improving livestock and human health.

According to the Ministry of Science and Technology, antiviral drugs are developed by directly targeting certain viral proteins.

However, this strategy often fails due to the rapid generation of drug-resistant viruses. Unlike higher organisms, a viral polymerase—the viral enzyme that synthesizes its nucleic acid (RNA)—does not have proofreading capacity.

The RNA viruses such as the coronaviruses do not have the mechanisms to remove wrongly incorporated nucleotides (building blocks of viral RNA) during the synthesis of the viral genome.

The lack of proofreading capacity results in the accumulation of point mutations in the viral genome. This leads to changes in viral proteins. The altered viral proteins may then become resistant to the available antiviral drugs.

This intriguing ability of the viruses to rapidly and frequently change themselves is a big challenge for the scientists in developing anti-viral drugs.

Viruses can only replicate inside the host cell. A host (human) cell contains around 25,000 proteins. During replication, viruses establish numerous interactions with these cellular proteins. A virus needs more than 1,000 different cellular proteins to replicate inside the host cell effectively.

Dr Naveen Kuman, the scientist at NCVTC, is exploring an alternate strategy to target such cellular proteins, protein-protein (virus-host) interaction and epigenetic regulators for anti-viral drug development commonly called as host-directed antiviral therapy.

These anti-virals are believed to have fewer tendencies in inducing drug resistance because it is not possible for the virus to easily change missing cellular functions by mutations.