Introduction: The major variant of concerns has shared mutations in severe acute respiratory SARS-CoV-2 spike proteins, mostly on the S1 unit, which resulted in a higher transmissibility rate and affect viral virulence and clinical outcome. The spike protein mutations and other non-structural protein mutations in the VOCs may lead to escape approved vaccinations. Nanobodies, single-domain fragments of camelid heavy-chain antibodies, have been developed to target a wide variety of viruses, frequently with the goal of using them as therapeutic agents. it has shown antiviral properties in various challenges with high affinity blocking SARS-CoV-2 spike interaction with ACE2 protein. A new strategy that allows the rapid and efficient engineering of mono- and multi-specific trivalent antibodies. reformatting nanobodies into multivalent constructs has been proposed to have a number of advantages for such antiviral purposes, including the potential to prevent conformational changes required for the virus to infect host cells.
Methods: In this review, we used online databases such as NCBI (PubMed), and google scholar. This research is the result of a survey of more than 50 articles, of which 26 articles were directly used in this study.
Results: SARS-CoV-2 is a positive-sense single-stranded RNA virus whose genome is of low stability thus is more prone to mutation accumulation, with approximately 9.8×10-4 annual substitutions/site. The S1 unit possesses the receptor-binding domain (RBD), which can directly bind to the ACE2 receptor and there is also the dominant target of neutralizing antibodies against SARS-CoV-2. S1 is thus considered a hotspot for mutations that may have high clinical relevance in terms of virulence, transmissibility, and host immune monomers that each avidly bind an RBD with an extreme combination of escape mutations. Nanobody multimerization has been shown to improve target affinity by avidity. In the case of Nb6 and mNb6, the structure-guided design of a multimeric construct that simultaneously engages all three RBDs yielded profound gains in potency. Furthermore, because RBDs must be in the upstate to engage with ACE2, conformational control of RBD accessibility serves as an added neutralization mechanism. Indeed, when mNb6-tri engages with Spike, it prevents ACE2 binding both by directly occluding the binding site and by locking the RBDs into an inactive conformation.
Conclusion: An outbreak of COVID-19 in Iran has spread throughout the country. Since the medical resources are limited, here, we aimed to identify the urgent issues that the world must consider to develop safe and effective preventions and therapeutics.