Our study reports that this process, while effective, may be missing out on crucial contributions from other viral proteins. To support this, we showed that when the virus’ nucleocapsid (N) protein is included during the process, the resulting viruses are significantly more infectious.
The study design involved producing pseudoviruses that were enveloped by the spike protein, and also packaged a green fluorescent protein, which gets expressed when the virus infects a target cell. From an initial panel of twenty-four viral proteins of the SARS CoV-2, we individually generated pseudoviruses in the presence of each, and checked the infectivity levels. The N protein clearly emerged as the most significant enhancer of infection. Following this, we developed a synthetic microbody, which could interfere with the virus’ invasion of cells, thereby blocking the infection. When tested with this, regular pseudoviruses were rapidly rendered ineffectual by the microbody. However, those boosted by the N protein required a markedly higher amount of this neutralizing agent to restrict the infection.
Finally, we deduced that the likely explanation for this effect was because the N protein could bring about a higher incorporation of the spike protein into individual viral particles. This effectively meant that each viral particle was now much more capable of binding to and invading a target cell, because it simply had more spike protein present on the surface.
The immediate impact of this study would be to help design more robust experiments for screening therapeutic drugs, neutralizing antibodies, etc. against the SARS CoV-2. This also advocates the case for including the N protein in vaccine preparations, especially for viral vector-based vaccines, which could help the vaccination provoke more effective responses from our body’s immune system.
