COVID-19 is caused by the coronavirus SARS-CoV-2, which jumped into the human population in late 2019 from a currently uncharacterised animal reservoir. Due to this recent association with humans, SARS-CoV-2 may not yet be fully adapted to its human host. This has led to speculations that SARS-CoV-2 may be evolving towards higher transmissibility. The most plausible mutations under putative natural selection are those which have emerged repeatedly and independently (homoplasies). Here, we formally test whether any homoplasies observed in SARS-CoV-2 to date are significantly associated with increased viral transmission. To do so, we develop a phylogenetic index to quantify the relative number of descendants in sister clades with and without a specific allele. We apply this index to a curated set of recurrent mutations identified within a dataset of 46,723 SARS-CoV-2 genomes isolated from patients worldwide. We do not identify a single recurrent mutation in this set convincingly associated with increased viral transmission. Instead, recurrent mutations currently in circulation appear to be evolutionary neutral and primarily induced by the human immune system via RNA editing, rather than being signatures of adaptation. At this stage we find no evidence for significantly more transmissible lineages of SARS-CoV-2 due to recurrent mutations.

/pdf/no-evidence-for-increased-transmissibility-from-recurrent-3b6es0n879.pdf

No evidence for increased transmissibility from recurrent mutations in SARS-CoV-2.

mRNA vaccines have tremendous potential to fight against cancer and viral diseases due to superiorities in safety, efficacy and industrial production. In recent decades, we have witnessed the development of different kinds of mRNAs by sequence optimization to overcome the disadvantage of excessive mRNA immunogenicity, instability and inefficiency. Based on the immunological study, mRNA vaccines are coupled with immunologic adjuvant and various delivery strategies. Except for sequence optimization, the assistance of mRNA-delivering strategies is another method to stabilize mRNAs and improve their efficacy. The understanding of increasing the antigen reactiveness gains insight into mRNA-induced innate immunity and adaptive immunity without antibody-dependent enhancement activity. Therefore, to address the problem, scientists further exploited carrier-based mRNA vaccines (lipid-based delivery, polymer-based delivery, peptide-based delivery, virus-like replicon particle and cationic nanoemulsion), naked mRNA vaccines and dendritic cells-based mRNA vaccines. The article will discuss the molecular biology of mRNA vaccines and underlying anti-virus and anti-tumor mechanisms, with an introduction of their immunological phenomena, delivery strategies, their importance on Corona Virus Disease 2019 (COVID-19) and related clinical trials against cancer and viral diseases. Finally, we will discuss the challenge of mRNA vaccines against bacterial and parasitic diseases.

/pdf/mrna-vaccine-a-potential-therapeutic-strategy-3kqr8ovmwv.pdf

mRNA vaccine: a potential therapeutic strategy.

Genetics and genomics of SARS-CoV-2: A review of the literature with the special focus on genetic diversity and SARS-CoV-2 genome detection

Determining the transmissibility, prevalence and patterns of movement of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is central to our understanding of the impact of the pandemic and to the design of effective control strategies. Phylogenies (evolutionary trees) have provided key insights into the international spread of SARS-CoV-2 and enabled investigation of individual outbreaks and transmission chains in specific settings. Phylodynamic approaches combine evolutionary, demographic and epidemiological concepts and have helped track virus genetic changes, identify emerging variants and inform public health strategy. Here, we review and synthesize studies that illustrate how phylogenetic and phylodynamic techniques were applied during the first year of the pandemic, and summarize their contributions to our understanding of SARS-CoV-2 transmission and control. In this Review, the authors describe how phylogenetic and phylodynamic methods provide insight into viral evolution, focusing on the SARS-CoV-2 pandemic. The approaches reveal routes and timings of transmission events, and they can assess the effectiveness of various intervention measures aimed at controlling the virus. 

/pdf/phylogenetic-and-phylodynamic-approaches-to-understanding-245r1fim.pdf

Phylogenetic and phylodynamic approaches to understanding and combating the early SARS-CoV-2 pandemic

Mutations of SARS-CoV-2 spike protein: Implications on immune evasion and vaccine-induced immunity.

Large-scale re-engineering of synonymous sites is a promising strategy to generate vaccines either through synthesis of attenuated viruses or via codon optimized genes in DNA vaccines. Attenuation typically relies on de-optimisation of codon pairs and maximization of CpG dinucleotide frequencies. So as to formulate evolutionarily-informed attenuation strategies that aim to force nucleotide usage against the direction favoured by selection, here we examine available whole-genome sequences of SARS-CoV-2 to infer patterns of mutation and selection on synonymous sites. Analysis of mutational profiles indicates a strong mutation bias towards U. In turn, analysis of observed synonymous site composition implicates selection against U. Accounting for dinucleotide effects reinforces this conclusion, observed UU content being a quarter of that expected under neutrality. Possible mechanisms of selection against U mutations includes selection for higher expression, for high mRNA stability or lower immunogenicity of viral genes. Consistent with gene-specific selection against CpG dinucleotides, we observe systematic differences of CpG content between SARS-CoV-2 genes. We propose an evolutionarily-informed approach to attenuation that, unusually, seeks to increase usage of the already most common synonymous codons. Comparable analysis of H1N1 and Ebola finds that GC3 deviated from neutral equilibrium is not a universal feature, cautioning against generalization of results.

/pdf/evidence-for-strong-mutation-bias-towards-and-selection-2pu8pe5qgm.pdf

Evidence for strong mutation bias towards, and selection against, U content in SARS-CoV-2: implications for vaccine design.

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Evidence for strong mutation bias towards, and selection against, U content in SARS-CoV-2: implications for vaccine design.