About 30% of all respiratory tract infections are caused by coronaviruses, leading to widespread illnesses and, in some cases, to epidemic and even pandemic outbreaks, as we experienced with the COVID-19 pandemic. Despite the development of groundbreaking technology that enables the design of prophylactic vaccines, access to those vaccines is not equal across the globe, especially in low-resource countries, and also other hesitations prevent their adoption.

In addition, coronavirus variants are emerging that can have higher infectivity and resistance to existing vaccines and antiviral treatments. Therefore, fast-acting antiviral drugs with broad activity against multiple respiratory coronaviruses and the ability to be rapidly distributed as oral treatments are urgently needed.

AI-Powered Drug Development

In 2020, at the beginning of the COVID-19 pandemic, a multidisciplinary team at the Wyss Institute for Biologically Inspired Engineering at Harvard University used AI tools to develop a broad-spectrum antiviral drug. Led by Wyss Founding Director Donald Ingber, M.D, Ph.D., the team leveraged computational and biological modeling capabilities to repurpose existing FDA-approved drugs for fighting the disease.

By utilizing AI-enabled molecular modeling, the team identified the drug bemcentinib as a potential antiviral agent. With further optimization, they developed a more specific and effective antiviral drug with efficacy against a broad range of coronaviruses.

Targeting Hidden Regions

Unlike other research groups targeting external surfaces of Spike proteins, the team focused on hidden regions of the Spike protein. By identifying specific sites within the protein, they aimed to prevent membrane fusion and viral entry, effectively inhibiting virus replication.

Through computational screening of existing drugs, bemcentinib was identified as a potent inhibitor of SARS-CoV-2 infection. Novel compounds were then designed to enhance antiviral activity, resulting in WYS-694, a highly potent antiviral compound.

Promising Results

WYS-694 demonstrated significant inhibition of SARS-CoV-2 infection in mice, showing great promise as an oral prophylactic treatment. The team's integrated approach of AI-driven computational and experimental technologies has paved the way for developing drugs against various virus families.

Future Implications

Senior author Donald Ingber highlighted the potential of this approach in dealing with future viral outbreaks. The newly developed drug not only shows promise for respiratory pandemics but also for combating other virus families utilizing membrane fusion proteins.

Source: Technology Networks