How to mix the best anti-SARS-CoV-2 cocktail

Neutralisation resistance generated by Spike (S) protein mutations in Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) poses a challenge to antibody therapies for COVID-19. Antibody cocktails targeting the S protein receptor binding domain (RBD) are one way to avoid viral neutralisation escape, however only certain antibody combinations are currently effective. Here, Dr Zhiqiang Ku shares insight into his team’s development of a unique antibody cocktail with neutralising activity against COVID-19.

Antibodies have emerged as important tools in the global fight against SARS‑CoV-2. Therapeutic antibodies targeting the S protein of SARS-CoV-2 can curb disease progression in individuals with asymptomatic or mild COVID-19. They can also act as a prophylaxis in cases of potential exposure.

The first step of SARS-CoV-2 infection involves docking of the viral S protein at the cellular receptor angiotensin-converting enzyme 2 (ACE2). The hot spots on the S protein that directly interact with ACE2 are concentrated in the RBD, making it the leading target for antibody intervention. Unsurprisingly, SARS‑CoV-2-neutralising antibodies isolated from COVID-19 patients predominantly target the RBD. Understanding the molecular determinants of the interaction between the RBD and neutralising antibodies is therefore vital to antibody therapeutics and vaccine design.