There have been over 7 million cases and almost 413,372 deaths globally due to the novel coronavirus (2019‐nCoV) associated disease COVID‐19, as of June 11, 2020. Phylogenetic analysis suggests that there is a common source for these infections. The overall sequence similarities between the spike protein of 2019‐nCoV and that of SARS‐CoV are known to be around 76‐78% and 73‐76% for whole protein and receptor‐binding domain (RBD), respectively. Thus, they have the potential to serve as drug and/ or vaccine candidate. However, the individual response against 2019‐nCoV differs due to genetic variations in the human population. Understanding the variations in Angiotensin‐converting enzyme 2 (ACE2) and human leukocyte antigen (HLA) that may affect the severity of 2019‐nCoV infection could help in identifying individuals at higher risk from the COVID‐19. A number of potential drugs/vaccines as well as antibody/cytokine‐based therapeutics are running in various developmental stages of preclinical/clinical trials against SARS‐CoV, MERS‐CoV and 2019‐nCoV with substantial cross‐reactivity, which may be used against COVID‐19. For diagnosis, reverse transcription polymerase chain reaction (RT‐PCR) is the gold standard test for initial diagnosis of COVID‐19. Kit based on serological tests are also recommended for investigating the spread of COVID‐19 but it is challenging due to antibodies cross‐reactivity. This review comprehensively summarizes the recent reports available regarding the host‐pathogen interaction, morphological and genomic structure of the virus, and the diagnostic techniques as well as available and potential therapeutics against COVID‐19.
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Background: In the current scenario, designing of world-wide effective malaria vaccine against Plasmodium falciparum remain challenging despite the significant progress has been made in last few decades. Conventional vaccinology (isolate, inactivate and inject) approaches are time consuming, laborious and expensive; therefore, the use of computational vaccinology tools are imperative, which can facilitate the design of new and promising vaccine candidates. Results: In current investigation, initially 5548 proteins of P. falciparum genome were carefully chosen for the incidence of signal peptide/ anchor using SignalP4.0 tool that resulted into 640 surface linked proteins (SLP). Out of these SLP, only 17 were predicted to contain GPI-anchors using PredGPI tool in which further 5 proteins were considered as malarial antigenic adhesins by MAAP and VaxiJen programs, respectively. In the subsequent step, T cell epitopes of 5 genome derived predicted antigenic adhesins (GDPAA) and 5 randomly selected known malarial adhesins (RSKMA) were analysed employing MHC class I and II tools of IEDB analysis resource. Finally, VaxiJen scored T cell epitopes from each antigen were considered for prediction of population coverage (PPC) analysis in the world-wide population including malaria endemic regions. The validation of the present in silico strategy was carried out by comparing the PPC of combined (MHC class I and II) predicted epitope ensemble among GDPAA (99.97%), RSKMA (99.90%) and experimentally known epitopes (EKE) of P. falciparum (97.72%) pertaining to world-wide human population.
Conclusions:The present study systematically screened 5 potential protective antigens from P. falciparum genome using bioinformatics tools. Interestingly, these GDPAA, RSKMA and EKE of P. falciparum epitope ensembles forecasted to contain highly promiscuous T cell epitopes, which are potentially effective for most of the world-wide human population with malaria endemic regions. Therefore, these epitope ensembles could be considered in near future for novel and significantly effective vaccine candidate against malaria.
Human malaria is a pathogenic disease mainly caused by Plasmodium falciparum, which was responsible for about 405,000 deaths globally in the year 2018. To date, several vaccine candidates have been evaluated for prevention, which failed to produce optimal output at various preclinical/clinical stages. This study is based on designing of polypeptide vaccines (PVs) against human malaria that cover almost all stages of life-cycle of Plasmodium and for the same 5 genome derived predicted antigenic proteins (GDPAP) have been used. For the development of a multi-immune inducer, 15 PVs were initially designed using T-cell epitope ensemble, which covered N99% human population as well as linear B-cell epitopes with or without adjuvants. The immune simulation of PVs showed higher levels of T-cell and B-cell activities compared to positive and negative vaccine controls. Furthermore, in silico cloning of PVs and codon optimization followed by enhanced expression within Lactococcus lactis host system was also explored. Although, the study has sound theoretical and in silico findings, the in vitro/in vivo evaluation seems imperative to warrant the immunogenicity and safety of PVs towards management of P. falciparum infection in the future.
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