The parasite Plasmodium falciparum, responsible for the most deadly form of human malaria, is one of the extremely AT-rich genomes sequenced so far and known to possess many atypical characteristics. Using multivariate statistical approaches, the present study analyzes the amino acid usage pattern in 5038 annotated protein-coding sequences in P. falciparum clone 3D7. The amino acid composition of individual proteins, though dominated by the directional mutational pressure, exhibits wide variation across the proteome. The Asn content, expression level, mean molecular weight, hydropathy, and aromaticity are found to be the major sources of variation in amino acid usage. At all stages of development, frequencies of residues encoded by GC-rich codons such as Gly, Ala, Arg, and Pro increase significantly in the products of the highly expressed genes. Investigation of nucleotide substitution patterns in P. falciparum and other Plasmodium species reveals that the nonsynonymous sites of highly expressed genes are more conserved than those of the lowly expressed ones, though for synonymous sites, the reverse is true. The highly expressed genes are, therefore, expected to be closer to their putative ancestral state in amino acid composition, and a plausible reason for their sequences being GC-rich at nonsynonymous codon positions could be that their ancestral state was less AT-biased. Negative correlation of the expression level of proteins with respective molecular weights supports the notion that P. falciparum, in spite of its intracellular parasitic lifestyle, follows the principle of cost minimization.

The genome/proteome composition of Bdellovibrio bacteriovorus, the predatory microorganism that preys on other Gram-negative bacteria, has been analyzed. The study elucidates that translational selection plays a major role in genome compositional variation with higher intensity compared to other deltaproteobacteria. Other sources of variations having relatively minor contributions are local GC-bias, horizontal gene transfer and strand-specific mutational bias. The study identifies a group of AT-rich genes with distinct codon composition that is presumably acquired by Bdellovibrio recently from Gram-negative prey-bacteria other than deltaproteobacteria. The proteome composition of this species is influenced by various physico-chemical factors, viz, alcoholicity, residue-charge, aromaticity and hydropathy. Cell-wall-surface-anchor-family (CSAPs) and transporter proteins with distinct amino acid composition and specific secondary-structure also contribute notably to proteome compositional variation. CSAPs, which are low molecular-weight, outer-membrane proteins with highly disordered secondary-structure, have preference toward polar-uncharged residues and cysteine that presumably help in prey-predator interaction by providing particular bonds of attachment.

Comparative analyses of codon/amino acid usage in Leishmania major, Trypanosoma brucei and Trypanosoma cruzi reveal that gene expressivity and GC-bias play key roles in shaping the gene composition of all three parasites, and protein composition of L. major only. In T. brucei and T. cruzi, the major contributors to the variation in protein composition are hydropathy and/or aromaticity. Principle of Cost Minimization is followed by T. brucei, disregarded by T. cruzi and opposed by L. major. Slowly evolving highly expressed gene-products of L. major bear signatures of relatively AT-rich ancestor, while faster evolution under GC-bias has characterized the lowly expressed genes of the species by higher GC 12 -content.

Dengue virus is a mosquito-borne human pathogen, causing disease that ranges from mild febrile illness to life-threatening hemorrhage fever/ shock syndrome. The altered antigenicity and virulence in the dengue virus, resulting from the accumulation and fixation of the favorable mutations in the genome, is the cause of concern nowadays. The present study focuses on the comparative study of polyproteins of viral strains within each dengue serotype to understand the trend of intra-serotype polyprotein variation and its effect on the antigenicity. Polyprotein sequences of viral strains in each serotype were investigated using multivariate statistical analysis, phylogenetic analysis and multiple sequence alignment methods. Epitope prediction was done by Bepipred-1.0 server and experimental epitope data were extracted from Immune Epitope Database with BLAST search. The study reveals that the polyproteins of viral strains of a serotype have variable amino acid composition that corresponds to the geographical regions of origin. This compositional variation has occurred due to the presence of polymorphic residues at different positions along the polyprotein sequence. The polymorphic residues have also been identified at epitope regions of structural proteins as well as NS1 of viral strains, possessing dissimilar physicochemical properties and occupy surface accessible positions. These positions on epitopes with polymorphic, dissimilar and surface accessible residues might act as putative sites for generation of antigenic variation among viral strains of a serotype of different geographical origin. Thus, these polymorphic residue positions on epitopes might be considered as putative target for development of drug or vaccine, in future.

The highly contagious disease COVID-19, caused by SARS-CoV-2, has emerged as a global pandemic. The high rate of contact transmission of this virus is the major cause of concern nowadays. Owing to the absence of any effective drugs/vaccines against COVID-19, many countries adopted ‘lockdown’ to minimize transmission of virus. The other means that was applied during lockdown, to mitigate the growth of infection is the ‘test, trace, track and isolate’. However, different countries responded differently to these control measures with different outcome in the growth of infection. For now, several countries have started ‘unlock’, to handle the severe economic stress, created in response to lockdown. Again, lifting lockdown is another global threat, having the chance of second wave of infection. In such situation, the major challenge is to prevent the spread of infection, amid resumption of work. The present review is aimed to outline the prospect and future direction of disease management and current therapeutics against COVID-19.