PCOM Georgia faculty members, including (L-R) Shashidharamurthy Taval, PhD, Srujana Rayalam, DVM, PhD, and Vicky Mody, PhD, are investigating various strategies for the prevention and treatment of COVID-19.

Three department of pharmaceutical sciences associate professors at PCOM Georgia, each with their own expertise, along with doctoral, graduate and high school students and research assistants, have joined forces to investigate various strategies for the prevention and treatment of COVID-19.

The faculty members include Shashidharamurthy Taval, PhD, Vicky Mody, PhD, and Srujana Rayalam, DVM, PhD. The team had a paper published recently on their research in Communications Biology, an open access journal that publishes research, reviews and commentary in the biological sciences.

Dr. Taval, who is an immunologist by training, became interested in the virus initially due to the unique immunological responses seen in patients affected by COVID-19. His biochemistry background equipped him to investigate the viral genome replication and conceive of the idea of COVID-19 virus – specific enzymes as potential drug targets. He collaborated with Dr. Mody, a medicinal chemist, and Dr. Rayalam, a pharmacologist and veterinarian, to get the project started.

Dr. Mody said, “Although global vaccination is currently underway, with new variants emerging, the efficacy of immunization to provide protection against the newer strains needs to be thoroughly investigated which could be a time-consuming process.

He added, “Currently, there are no anti-COVID-19 specific FDA-approved drugs either for the treatment of COVID-19 or to help prevent viral spread. Therefore, there is an urgent need to identify and develop potential therapeutics to prevent the pathogenesis and rapid spread of the infection.”

The team is studying FDA-approved drugs that could be repurposed to inhibit enzymes called 3CLpro and PLpro that affect the replication of the COVID-19 causing virus. These two enzymes are known to speed up the breakdown of the viral protein chain into smaller, more mature proteins that are required for the replication of the virus.

During the past 18 months, the team used computational molecular modeling to screen almost 4,000 FDA-approved drugs. From this group, 47 drugs were selected to study their inhibitory effects on purified viral enzymes. The results indicate that six of the drugs reduced enzymatic activity.

Drugs that Potentially Silence the Replication of the COVID-19 Causing Virus

These drugs include boceprevir and ombitasvir prescribed for the treatment of Hepatitis C, paritaprevir, another drug that shows promise for the treatment of Hepatitis C, tipranavir, which is used to treat HIV, micafungin, an anti-fungal agent, and ivermectin, effective against parasitic roundworms.

Dr. Mody said the drugs are, for the most part, unrelated.

Dr. Rayalam added, “Our studies show possible mechanism of these agents against COVID-19, but we believe that additional studies are needed to confirm our results. It is imperative that we conduct pre-clinical and clinical studies to assess the safety and efficacy of all of these drugs in inhibiting the replication of the COVID-19 causing virus.”

Dr. Taval said, “This research could be useful in developing highly specific, therapeutically viable drugs to inhibit COVID-19 causing virus replication either alone or in combination with drugs specific for other COVID-19 viral targets.”

Drug Discovery and Development

As the team works to develop new drugs to treat COVID-19, pre-clinical studies with newly developed, small molecular-weight molecules are planned. In addition, the team is developing an inhaled formulation to deliver drugs directly to the airways where most respiratory viruses colonize.

Studies are also being conducted to identify natural products derived from plants that have the potential to reduce the infectivity and spread of the COVID-19 causing virus through the inhibition of virus specific enzymatic activity.

The team members acknowledge that they have received support from both Mindy George-Weinstein, PhD, chief research and science officer, and Avadhesh C. Sharma, PharmD, PhD, chair and professor of the Department of Pharmaceutical Sciences, and are thankful to them.

Along with the faculty members, the team includes two research assistants, two PCOM Georgia biomedical sciences and five doctor of pharmacy students, and two high school student-volunteers from Lambert High School in Suwanee, Georgia.