With the rapid increase of deaths caused by the novel Coronavirus pandemic, efforts to develop a drug that can cure the disease has been the priority of drug scientists and researchers from all over the world. Amidst all these, several researchers from the US have cracked the mechanism which leads the SARS-CoV-2 virus to enter the host cell, transcribe and replicate without being detected by the innate immune system.
Dr Yogesh K. Gupta, a scientist of Indian origin at UT Health San Antonio has successfully decoded the camouflage mechanism through which Coronavirus enters the cells in hosts body without having to encounter the resistance of the immune system. “It’s camouflage. Because of the modifications, which fool the cell, the resulting viral messenger RNA is now considered as part of the cell’s code and not foreign” said he.
Dr Gupta was able to decipher the 3D structure of nsp16, which has paved the way to design drugs for the cure of novel Coronavirus SARS-CoV-2. The nsp16 protein is a type of S-adenosylmethionine – dependent protein, which can be activated only in the presence of nsp10. The drugs will be designed in a way that it inhibits nsp16 from modifying the host cells, and the immune system can pounce it, recognizing it as foreign.
Coronavirus SARS-CoV-2, as found in a study in Nature Communications, produces an enzyme known as the nsp16 to modify its messenger RNA cap and enter the cells. To understand better, just as a bugler hacks and deactivates all the alarm systems before intruding into a building, Coronavirus uses the same mechanism to grow in the host’s body.
The molecule nsp10 will be used to modify the mRNA’s to mimic the host cell’s own RNA’s. Coronavirus transcribes and replicates the genome using the non-structural nsp 1-16 proteins, which are capped to ensure translation, stability and evade the immune system of the host cell. Researchers were crystallizing the nsp10/16 complex and studied the structure at atomic resolution.
The study co-author, Dr Robert Hramos said “Dr Yogesh’s work discovered the 3D structure of a key enzyme of the COVID-19 virus required for its replication and found a pocket in it that can be targeted to inhibit that enzyme. This is a fundamental advance in our understanding of the virus”. According to the researchers from The University of Texas Health Science Centre, in the US, deciphering the 3D structure will be helpful in successful drug designing against the virus. The researchers also stated that the structural sites present on the surface of SARS-CoV-2 nsp 10 molecules could be targeted for antiviral development.