Like human antibodies, certain “nanobodies” can be found in Llamas, camels, and alpacas that are smaller in size, more stable and easier to produce. These nanobodies, just like antibodies, can detect and attach to certain protein cells and block them from entering other cells. Nanobodies have an advantage over human antibodies as they can bind to little pockets in the protein that larger antibodies might miss and also maintain their shape in extreme environments such as acid-filled stomach where antibodies are less sustainable. Recently, in a study published in the journal Nature Structural & Molecular Biology, scientists including those from the Rosalind Franklin Institute found that two of these Llama nanobodies can neutralize coronavirus.
Earlier, during the 2002-2003 SARS pandemic, human antibodies were used as immunotherapy. The process involved giving patients virus-free neutralizing agents-either from people previously infected with SARS or purified antibodies. The antibodies would block the binding of the virus with the other protein cells. The same was tested for the present infection of SARS-CoV-2, but the reaction wasn’t the same since the antibodies refused to block and bind.
However, when the nanobodies of llamas were tested and studied, two closely related nanobodies named “H11-H4” and ”H11-D4” blocked the attachment of the SARS-CoV-2 spike to ACE2 in cell culture. The scientists said that these nanobodies targeted a region of the protein “immediately adjacent to and slightly overlapping with the ACE2 binding region.” According to the analysis, both nanobodies have been shown to neutralize live SARS-CoV-2, with H11-H4 showing particularly high potency and human antibody additive neutralization. The scientists said the nanobodies could find application for passive immunization of patients with extreme COVID-19 either alone or in combination with other antibodies.
The llama nanobodies initially didn’t bind closely enough to the virus to prevent it from entering cells. The team mutated the nanobody section that binds to the spike protein before more snuggly latches onto the virus. They finally identified two nanobodies, which effectively prevented the virus from reaching human cells when exposed to SARS-CoV-2 in large amounts. Modifying old nanobodies only offers a solution for the short term. Scientists are also working on projects in which llama create from scratch their own nanobodies.
Even though Llama nanobodies can neutralize coronavirus infection in humans, there are still experiments and trials to be done. So for now, infected individuals can receive antibodies via plasma infusions from the blood of recovered COVID-19 patients during a process called passive immunization.