New Delhi: In what could pave the way for designing a potential drug for the deadly Nipah virus, a team of Indian scientists have identified a total of 150 inhibitory molecules which can block the activity of the virus proteins.
The new research, carried out by scientists from Indian Institute of Science Education and Research (IISER), Pune was published in the journal, PLOS Neglected Tropical Diseases.
First identified in 1999 in Malaysia, Nipah virus is transmitted to humans from bats and pigs and has a high mortality rate of more than 75% in Southeast Asia. As many as 72- 86% of individuals who were infected with the virus in Bangladesh and India had died.
In May 2018, the outbreak claimed lives of 21 of the 23 infected people in Kerala. Yet, two decades after the first outbreak, there are still no approved drugs or vaccines against the deadly disease.
As of now, its outbreaks are limited to Asia and the death toll during each outbreak has remained around 100. But, researchers worry that if no cure is found soon, the disease could become pandemic.
In the new research, the team, led by associate professor M.S. Madhusudhan from IISER, Pune, used the available information on the structure of the Nipah virus to identify 150 possible inhibitors of the virus. These inhibitors are basically molecules which can stop the virus from making proteins, eventually helping to get rid of the infection.
The team first made a three-dimension model of all the nine Nipah virus proteins (six structural, three non-structural), which are potential targets for rational drug design. Then, the researchers computationally designed four putative peptides inhibitors and 146 small molecule inhibitors and used them to block the activity of the proteins.
The efficacy of the proposed inhibitors was tested against the 15 different strains of the virus-- five from India, 7 from Malaysia and three from Bangladesh.
Finally, 13 of their proposed inhibitors were short-listed as the most promising because of their binding strength to the virus, stability, and effectiveness against multiple strains of Nipah virus.
"It is highly likely that the proposed inhibitors would be quite effective against all strains of the Nipah virus. They may even be useful for drug design in case of other related zoonotic viruses (which spread between animals and people) and pose a serious epidemic threat," the researchers said, highlighting that the computer-aided drug design can speed up the discovery of new bioactive compounds.
This method uses modern computational approaches to disover, develop and assess drugs or molecules which show similar biological activity, based on information of a set of reference structures which impact the target. These molecules are further tested to see if they can be utilized to design drugs.