Drug development vs repurposing
There is no specific drug available on the market to treat post-COVID-19 infection and many laboratories around the world are currently busy finding potential molecule candidates that could block the virus life cycle at different stages. As the virus may infect various organs inside the human body, multidrug treatment could be a better strategy to cure the disease efficiently. (1)
However new drug development generally takes a few years. Therefore, biotech and pharma companies put their interest in new technology development to produce medicines faster with reduced costs of goods or opt for existing drug repurposing to deliver on the market an efficient and safe treatment against COVID-19. Candidates among existing antivirals, inhibitors, antibiotics and much more others already entered late clinical trial phases. (1)
Free ACE2 - drug repurposing
A good example of repurposing is the use of free ACE2 which undergone clinical trials for the treatment of acute respiratory distress syndrome. Recombinant soluble ACE2 could compete with the host cell ACE2 membrane receptor, inhibit the attachment of the SARS-CoV-2 virus to the receptor that could continue to work properly. Experimental studies have been shown that recombinant soluble ACE2 significantly blocks the virus infection.(1)
In addition to conventional two-chain-structured antibodies, Camelids produce single-heavy-chain Ab with the smallest naturally-occurring antigen binding domain, the VHH Fragment.
Due to their small sizes (~15kDa), high tissue penetration, and stability, VHH antibody fragments can be used in therapy to bind epitopes that are hidden and deliver drugs on a specific site.
In the COVID-19 context, Jiangdong Huo et al. identified a neutralizing Llama nanobody that interacts with a high affinity to the receptor-binding domain (RBD) of the spike protein (Protein S) of SARS-CoV-2. This interaction blocks the bounding between Protein S and the human ACE2 receptor preventing the virus entry into the host cell. (2)
VHH nanobodies are considered a promising treatment for COVID-19 blocking the virus in its life cycle.
1) Drugs targeting various stages of the SARS-CoV-2 life cycle: Exploring promising drugs for the treatment of Covid-19.
Ramarao Poduri, Gaurav Joshi, Gowraganahalli Jagadeesh.
Cellular Signalling 74 (2020) 109721 – DOI: 1016/j.cellsig.2020.109721
2) Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2.
Jiangdong Huo et al.
Nature Structural & Molecular Biology volume 27, pages846–854(2020) - DOI:10.1038/s41594-020-0469-6