Marwah Karim, PhD
Advancing the Repurposing of Lapatinib to Combat COVID-19, Future Pandemic Coronaviral, and Other Emerging Viral Infections
Summary
The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has killed millions of people worldwide and has caused global public health emergencies. Although there are effective vaccines available to reduce COVID-19 severity, there is no effective treatment option available to treat the patients who are already infected with the virus. Most of the existing antiviral drugs target viral enzymes, typically providing a “one drug, one bug” approach that can lead to the emergence of viral resistance. Moreover, addressing viruses individually uses resources inefficiently and is not easily scalable to meet the large unmet need. Our goal is to overcome these challenges by developing host-targeted broad-spectrum antivirals that would provide protection against SARS-CoV-2 and readiness for future coronavirus outbreaks. We have recently discovered lapatinib, an approved anti-cancer epidermal growth factor receptor (ErbB) 1/2/4 inhibitor, that suppresses replication of SARS-CoV-2 and other unrelated viruses in human cell lines as well as in unique human lung organoid models with a high barrier to resistance. ErbB1/2 are known as key regulators of acute lung injury and fibrosis, and their inhibition protects mice from lung injury and mortality. We hypothesize that Pan-ErbB inhibition is a safe strategy, which not only suppresses viral infection, but also reduces inflammation, acute lung injury, and fibrosis by inhibiting ErbB-mediated signaling. The results of this project will contribute significantly to the knowledge of virus-host interactions critical for SARS-CoV-2 infection and pathogenesis in human lung organoid and animal models. If successful, our project will advance lapatinib, as a key therapeutic component into clinical studies in hospitalized patients with the goal of not only reducing viral replication but also preventing lung injury and long-term fibrosis.
The PhRMA Foundation Postdoctoral Fellowship will have a fundamental impact on my career path. As a woman scientist from a developing country, I recognize the impact of role models on empowering students to pursue careers in science. This fellowship will help me to be an independent researcher and hopefully transition into a tenure-track faculty position at an academic institution. I am very honored and grateful to the PhRMA Foundation for this support.
