New NIH Awards to the Eddy Arnold Lab for antiviral drug discovery

May 18, 2022
Xavi Ruiz and Eddy Arnold in CABM Atrium

Rutgers University chemist and structural biologist Eddy Arnold has spent 35 years battling against HIV, helping to discover two FDA-approved anti-AIDS drugs.  The COVID-19 pandemic felt like a “deja vu” for him, and he and his group quickly began to study the novel coronavirus SARS-CoV-2, along with many scientists around the world.  His team has focused on studies of how some of the SARS-CoV-2 proteins are assembled and produced, stages that are essential for viral replication. In particular, Arnold is studying the target of nirmatrelvir, which is the active ingredient of Paxlovid, the most effective oral treatment currently available.

As a postdoctoral scientist with Michael Rossmann at Purdue University, Eddy Arnold spearheaded a team that solved the structure of a common cold virus. Arnold came to Rutgers in 1987 and was the first faculty member hired at the newly founded Center for Advanced Biotechnology and Medicine (CABM) at Rutgers. Arnold remains a CABM Resident Faculty Member and serves as Board of Governors and Distinguished Professor in Chemistry and Chemical Biology. His training at Purdue laid the groundwork for his studies at CABM of HIV and other viruses.  Arnold had a strong conviction that crystal structures of the HIV reverse transcriptase (RT) enzyme could facilitate the discovery of drugs for AIDS, which was a lethal infection at that time.  The many types of structures of HIV RT obtained successfully by the Arnold group helped to drive the discovery of two drugs (riplivirine and etravirine), and by now six licensed medicines marketed by Johnson & Johnson for treatment of HIV/AIDS.

After two years of the COVID-19 pandemic, SARS-CoV-2 appears to be here to stay, and more options for treatment and to combat resistance to current drugs are needed.  It also is very likely that other dangerous viruses will emerge, and it is imperative to be prepared against new viruses with pandemic potential, especially RNA viruses. 

Aiming to get ahead of future pandemics, the NIH’s National Institute of Allergy and Infectious Diseases (NIAID) has awarded almost $600 million to establish nine Antiviral Drug Discovery (AViDD) Centers for Pathogens of Pandemic Concern.  The Arnold group is contributing to two of the nine centers: the “Rapidly Emerging Antiviral Drug Development Initiative – AViDD Center” led by coronavirologist Ralph Baric at UNC Chapel Hill, and the “QBI Coronavirus Research Group Pandemic Response Program,” led by molecular and systems biologist Nevan Krogan at UCSF.  Overall, these two centers encompass an exceptional array of experts to develop novel antivirals to combat a broad range of dangerous viruses.

According to Arnold, “We use powerful tools to study the structure of viruses in minute detail and elucidate how they work at the molecular level.  I’m excited that we can use such structural information to accelerate discovery of life-saving medicines that can thwart future pandemics.”

The Arnold group will use structural biology to discover novel molecules that halt the molecular machines (called polymerases) that copy the genome of the viruses. They seek new treatments aimed at SARS-CoV-2, and for flaviviruses such as the Dengue and Zika viruses, and enteroviruses that cause hand-foot-and-mouth disease, among others.  Francesc Xavier Ruiz, Ph.D., an Assistant Research Professor at CABM, is co-leading the Arnold laboratory effort.  At Rutgers since 2015, Ruiz has co-led Arnold group studies of HIV protein assembly and drug binding, and the more recent efforts on SARS-CoV-2 proteins. A biochemist and structural biologist, he focuses on understanding catalysis and inhibition of proteins involved in viral infections, cancer, and other human diseases. Dr. Xavier Ruiz said “I am very happy to use the skills I gained in the Arnold lab over these past seven years to help develop the new antiviral agents that are so urgently needed.”

The Arnold laboratory is collaborating on both AViDD grants with the group of Matthias Götte, Chair of Medical Microbiology & Immunology at the University of Alberta-Edmonton, in Canada.  Götte has studied polymerases from SARS-CoV-2, HIV, hepatitis C, and other deadly viruses.  Like Arnold, Götte was motivated to study viruses because of their critical implications for human health.  The award to the Arnold group totals $2.3 million for three years (and up to $3.8 million over five years, pending Congressional approval), with the aim to discover and develop novel antiviral treatments to combat COVID-19 and future pandemics that may be caused by RNA viruses.