ABSTRACT
Some studies in the literature show that viruses can affect bacteria directly or indirectly, and viruses use their own specific ways to do these interactions. Furthermore, it is said that bacteria are prone to attachment mammalian cells during a viral illness using their surface proteins that bind to host extracellular matrix proteins such as fibronectin, fibrinogen, vitronectin, and elastin. A recent study identified the cooperation between bacteria and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in silico, in vitro, and in vivo. Like this study, we hypothesized that more bacteria protein might help SARS-CoV-2 transport and attach to angiotensin-converting enzyme 2 (ACE2). The bacteria's outer membrane proteins (OMPs) we chose were not random; they had to be on the outer surface of the bacteria because these proteins on the outer surface should have a high probability of interacting with both the spike protein and ACE2. We obtained by using bioinformatics tools that there may be binding between both ACE2 and spike protein of these bacteria's OMPs. Protein-protein interaction results also supported our hypothesis. Therefore, based on our predicted results, these bacteria OMPs may help SARS-CoV-2 move in our body, and both find and attach to ACE2. It is expected that these inferences obtained from the bioinformatics results may play a role in the SARS-CoV-2 virus reaching host cells. Thus, it may bring a different perspective to studies on how the virus can infect host cells.
ABSTRACT
The long-lasting COVID-19 pandemic and increasing SARS-CoV-2 variants demand effective drugs for prophylactics and treatment. Protein-based biologics offer high specificity, yet their noncovalent interactions often lead to drug dissociation and incomplete inhibition. Here, we have developed covalent nanobodies capable of binding with SARS-CoV-2 irreversibly via a proximity-enabled reactive therapeutic (PERx) mechanism. A latent bioreactive amino acid (FFY) was designed and genetically encoded into nanobodies to accelerate the PERx reaction rate. Compared with the noncovalent wild-type nanobody, the FFY-incorporated covalent nanobodies neutralized both wild-type SARS-CoV-2 and its Alpha, Delta, Epsilon, Lambda, and Omicron variants with drastically higher potency. This PERx-enabled covalent-nanobody strategy and the related insights into increased potency can be valuable to developing effective therapeutics for various viral infections.
ABSTRACT
The rapid accumulation of mutations in the SARS-CoV-2 Omicron variant that enabled its outbreak raises questions as to whether its proximal origin occurred in humans or another mammalian host. Here, we identified 45 point mutations that Omicron acquired since divergence from the B.1.1 lineage. We found that the Omicron spike protein sequence was subjected to stronger positive selection than that of any reported SARS-CoV-2 variants known to evolve persistently in human hosts, suggesting a possibility of host-jumping. The molecular spectrum of mutations (i.e., the relative frequency of the 12 types of base substitutions) acquired by the progenitor of Omicron was significantly different from the spectrum for viruses that evolved in human patients but resembled the spectra associated with virus evolution in a mouse cellular environment. Furthermore, mutations in the Omicron spike protein significantly overlapped with SARS-CoV-2 mutations known to promote adaptation to mouse hosts, particularly through enhanced spike protein binding affinity for the mouse cell entry receptor. Collectively, our results suggest that the progenitor of Omicron jumped from humans to mice, rapidly accumulated mutations conducive to infecting that host, then jumped back into humans, indicating an inter-species evolutionary trajectory for the Omicron outbreak.