Animal and human RNA viruses: genetic variability and ability to overcome vaccines

Abstract

RNA viruses, in general, exhibit high mutation rates; this is mainly due to the low fidelity displayed by the RNA-dependent polymerases required for their replication that lack the proofreading machinery to correct misincorporated nucleotides and produce high mutation rates. This lack of replication fidelity, together with the fact that RNA viruses can undergo spontaneous mutations, results in genetic variants displaying different viral morphogenesis, as well as variation on their surface glycoproteins that affect viral antigenicity. This diverse viral population, routinely containing a variety of mutants, is known as a viral 'quasispecies'. The mutability of their virions allows for fast evolution of RNA viruses that develop antiviral resistance and overcome vaccines much more rapidly than DNA viruses. This also translates into the fact that pathogenic RNA viruses, that cause many diseases and deaths in humans, represent the major viral group involved in zoonotic disease transmission, and are responsible for worldwide pandemics.

Identification of Cross-Reactive CD8+ T Cell Receptors with High Functional Avidity to a SARS-CoV-2 Immunodominant Epitope and Its Natural Mutant Variants

“…Hence, our data evidenced that the N 361-369 -specific TCRs had high affinity and functional avidity, both of which were key features to induce sufficient levels of T cell activation for antivirus responses. As a newly emerged single stranded RNA virus belonging to the highly contagious coronavirus subfamily, SARS-CoV-2 has a tendency to accumulate mutations over time (Duffy, 2018; Villa et al, 2020). Here, another innovative piece of our finding was that the 2 distinct N 361-369 -specific TCRs could recognize multiple N 361-369 mutations in complementary (Figure 4B).…”

“…Hence, the functional avidity of TCRs is a critical parameter to be evaluated for determining the pMHC recognition and posterior T-cell activation, which is essential for the killing of virus-infected cells and effective viral clearance (Campillo-Davo et al, 2020). On the other hand, RNA viruses have a tendency to accumulate mutations over time (Duffy, 2018; Villa et al, 2020), which present challenges for T cell-based vaccine development. Therefore, it is important to identify predominant epitopes together with diverse TCRs carrying broader cross-reactivity to SARS-CoV-2 and its mutant variants, which can provide detailed information to understand the mechanisms of T cell-mediated viral clearance in COVID-19 patients.…”

Invariant in variants

“…The tiny virus has been causing big trouble and keeps changing into various mutants, of which at least ten variants (α, β, γ, δ, η, ι, κ, λ, μ, o) have been designated by WHO up to Nov 26, 2021, all of which have been bringing so much sickness, injury and death to mankind [4] , [5] . The human immune system could mostly conquer the invasive coronavirus autonomously with the aid of effective vaccine, although which require continuing update of the vaccines to produce enough antibody [6] , [7] , [8] . Or else, we could actively deactivate the coronavirus in the ambient air [9] surrounding animals and human beings to largely suppress the infection probability.…”

Synthesis of Hetaryl-Substituted Asymmetric Porphyrins and Their Affinity to SARS-CoV-2 Helicase

“…The nature of coronavirus bearing a positive single-strand RNA genome is a further complication hindering the development of the antiviral drugs. Single-strand RNA viruses are very labile and readily mutate during replication and transcription phases [5][6][7][8], therefore it is almost impossible to develop a drug exhibiting high selectivity and affi nity with respect to RNA. This is the case of the viruses of Ebola hemorrhagic fever, SARS, AIDS, hydrophobia, hepatitis C and Е, West Nile encephalitis, and poliomyelitis, which have remained severe issues over several decades.…”

“…The possibility of helicase photooxidation under the action of porphyrins 1a-1c should depend on the photoactivity of the porphyrin as well as the presence of the amino acid residues prone to the photooxidation and their distance from the porphyrin. These amino acids include cysteine, methionine, tryptophane, tyrosine, and histidine; rate constant of their reaction with 1 O 2 equals 8.9×10 6 , 1.6×10 7 , 3.0×10 7 , 8×10 6 , and 3.2×10 7 mol -1 L s -1 , respectively [28]. The distance which reactive singlet oxygen can pass in the virus protein can hardly be estimated.…”