Development of TMPRSS2 Antibody as an Antiviral Treatment for SARS-CoV-2 (COVID-19)
Abstract
In early 2020, a new virus began generating headlines all over the world because of the unprecedented speed of its transmission. This new virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease (COVID-19), was first reported in December 2019 in Wuhan, China and continued to spread worldwide. COVID-19 has been responsible for over 4.8 million infections globally, causing more than 300,000 deaths. The United States is the most affected country. This is even more relevant to military personnel, who usually need to live and work in close quarters, which increases the chance of spreading the virus. To date, there is no approved treatment for COVID-19; thus, doctors can only treat the symptoms with supportive care, not the virus itself. Scientists are working on vaccines, which remain the most effective method to protect the general population from a viral infection. However, vaccines still require some time to be developed and even more for production and mass distribution. Antivirals, on the other hand, are likely to be developed and approved faster. Furthermore, an effective therapeutic approach would greatly benefit the population that is currently affected by the virus. Thanks to recent studies, we know which “door” (a receptor called ACE2) and “key” (a protease called TMPRSS2) the virus uses on the hosts to enter cells. Studies have also shown that ACE2 and TMPRSS2 are largely expressed in lung cells. In order to find an effective treatment against COVID-19, we aim to develop an efficient antiviral to block the entrance of the virus into lung cells. Our goal is to remove the “key” so the virus cannot open the “door” and enter host cells. To do this, we will use a unique cell model and the highly specific antibodies against TMPRSS2 that we developed in our laboratory. We will make lung cells and mini-lungs using human stem cells. We use chemical cues that our body uses for lung development to guide the stem cells becoming lungs. Using this method, we are able transform these stem cells into either two-dimensional monolayer lung cells or three-dimensional lung “organoids,” aka “mini-lungs in a dish.” These cultures contain different cell types found in the human lung, mimic closely the structure of the lung, and have been successfully used to study several viral infections. The unique properties of our lung cultures make them an ideal model to study COVID-19 and test if we can use TMPRSS2 antibodies to block virus entering our lung cells. After we have lung cells, we will first test if TMPRSS2 antibodies are toxic to the cells. Once we find a safe dose to use the antibodies, we will investigate if they can block virus entering lung cells. We will also investigate how the TMPRSS2 antibodies block virus entry to lung cells. We suspect they either reduce TMPRSS2 amount on cell surface so viruses do not have enough keys to enter cells or they block the function of TMPRSS2 (break the key) so viruses do not have functional keys to enter cells. Lastly, we will transform the TMPRSS2 antibodies that can safely be used in humans and test their efficacy and safety using our mini-lungs and animals. Our work has the potential of impacting, in a short time, the life of millions of individuals affected by COVID-19, and it will greatly improve respiratory health and provide a potential treatment for emerging viral diseases.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110070
Entities
People
- Ya-Wen Chen
Organizations
- United States Army
- University of Southern California