When Pharmaceutical Sciences Assistant Professor Anil Singh was invited to give a talk about inflammation at the start of the pandemic, he could not have known it would lead to new COVID-19 research.
While reading about the disease mechanism of COVID-19 in preparation for his talk, Singh noticed that many treatments used for COVID-19 are medications used to treat rheumatoid arthritis. When he dug a little deeper, Singh learned that the inflammation of the lungs during COVID-19 is clinically similar to the inflammation of synovial joints in rheumatoid arthritis.
“I made the connection over and over, and since my work is so closely tied into this kind of inflammation, I just wanted to explore it,” said Singh.
Singh assembled a team of researchers from Regeneron, Cornell University and Amity University to help him further investigate the connection and how it may lead to future COVID-19 therapeutics.
The team evaluated epigallocatechin-3-gallate (EGCG), a catechin found in green tea. Green tea has been widely researched in various pathologies and EGCG has previously been shown to have anti-inflammatory and antioxidant properties. One of the key strengths of catechins is their power to bind multiple proteins that may suppress the immune system response.
When a virus enters the human body, cells release interferon to tell the body to react and inhibit the viral replication. However, when the COVID-19 virus enters the human body, it dampens the body’s initial immune response.
“Your body does not realize it’s foreign,” explained Singh. “The virus highjacks the human immune system and goes into stealth mode.”
Once the virus is inside the cells, viral papain-like protease protein (PLPro) programs cells to interfere with the interferon response and prevent the body from mounting an antiviral response.
“The cells are literally hypnotized to make the viral proteins instead of interferon,” explained Singh.
The researchers used computer simulated experiments to evaluate various catechins and observed that EGCG showed a stronger binding affinity to PLPro, making it more effective in inhibiting PLPro protein activity. Their discovery was published as a peer-reviewed paper in the special issue of Catechins in Human Health 2020 of the journal Molecules of MDPI group, in February 2021. This proof of concept is a vital step in the development of clinical trials, several of which are now underway, paving the way to make EGCG a possible therapeutic option for COVID-19 prevention and treatment.
“It’s like the saying, ‘A journey of a thousand miles begins with a single step,’” said Singh, “it’s just a step and there are many now.”
With the emergence and rapid spread of new and potent variants of the virus and on-going challenges in the availability of vaccines worldwide, the development of additional therapeutics to combat the virus remains of the utmost importance to Singh.
“While we know vaccines are the best way to prevent serious risk of COVID-19, this study provides the rationale for development of small molecule inhibitors which could work as adjunct therapy along with vaccination as a way to treat COVID-19,” said Singh. “I thought it was my responsibility to let the world know what I know.”