PhD Scientific Days 2022

Translational Medicine III.

Morphological Studies of SARS-CoV-2 Variants with Atomic Force Microscopy

Text of the abstract

Introduction: The shape of enveloped viruses can vary on a wider spectrum compared to non-enveloped viruses (capsid only) due to their structural composition. SARS-CoV-2 is an enveloped, pleomorphic, single-stranded RNA virus. The transmissibility and severity of the virus and disease depends heavily on the repector affinity of the spike (S) protein. The differences of the variants are caused mainly by the different single nucleotide polymorphisms that the S protein carries. Current researches focus on these S protein mutations and how these mutations effect the receptor affinity of the protein.
Aims: In our current work we tried to reveal some other, mainly morphological differences between the variants, and find out whether these differences are significant or not. The putative theoretic differences in shape are due to the fact that the other structural proteins (M, N, E) of the virions have different mutations within the variants, furthermore there are mutations within the non-structural proteins too.
Method: The study consisted of the comparison of three different SARS-CoV-2 variants with atomic force microscopy (AFM). The compared variants are: wild type (Wuhan-Hu-1-reference), the delta variant (B.1.617.2) and the alpha variant (B.1.1.7). The production and purification of the viruses were done under BSL 3. conditions in the National Public Health Center (NNK). For the AFM images, coronavirus particles were fixed onto modified mica surface.
Results: Our results show that the size of the variants and their interaction with the surface differs significantly. The alpha variant shows a significantly greater flattening compared to the other variants. The size of the alpha and delta variants are significantly smaller than the size of the wild type virus particle.
Conclusion: From these results it is seen that the variants with higher transmissibility tend to have a higher (effective surface) / (volume) ratio, and a higher (genetic material) / (volume) ratio. We think these properties might significantly effect the transmissibility of variants besides the effects of the S protein mutations. Nevertheless a smaller particle can be constructed from less material, supposedly within a smaller time interval.
Funding: This work was funded by grants from the Hungarian National Research, Development and Innovation Office (K124966).