Development of neutralizing nanobodies against SARS-CoV-2

点击翻译按钮获取中文摘要

In FY20, Dr Ho has evaluated the current status and challenges for developing antibody therapeutics targeting SARS-Cov-2 and wrote a review/perspective article [Ho Antibody Therapeutics 2020; PMID: 32566896]. SARS-CoV-2 gains entry to human cells through its spike (S) protein binding to angiotensin-converting enzyme 2 (ACE2). Therefore, the receptor binding domain (RBD) of the S protein is the primary target for neutralizing antibodies. Selection of broad-neutralizing antibodies against SARS-CoV-2 and SARS-CoV is attractive and might be useful for treating not only COVID-19 but also future SARS-related CoV infections. Broad-neutralizing antibodies have been reported to target a conserved region in the RBD of the S1 subunit. The S2 subunit required for viral membrane fusion might be another target. A cocktail strategy combining two (or more) antibodies that recognize different parts of the viral surface that interact with human cells might be the most effective. In FY2020, our pilot screen in the Ho lab using phage display technology has identified a panel of camel nanobodies that might recognize diverse conformations of the RBD. Some might bind an "open" conformation of the RBD, which might block the interaction with the ACE2 on human cell, while others might bind a "close" conformation, which might lock its conformation in the off state. Ongoing studies will establish our nanobodies as a new family of anti-viral drugs for treating COVID-19 and potentially future coronavirus infections in humans.