In December 2019, an outbreak of pneumonia of unknown origin was reported in Wuhan, Hubei Province, China. Pneumonia cases were epidemiologically linked to the Huanan Seafood Wholesale Market. Inoculation of respiratory samples into human airway epithelial cells, Vero E6 and Huh7 cell lines, led to the isolation of a novel respiratory virus whose genome analysis showed it to be a novel coronavirus related to SARS-CoV, and therefore named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a betacoronavirus belonging to the subgenus Sarbecovirus. The global spread of SARS-CoV-2 and the thousands of deaths caused by coronavirus disease (COVID-19) led the World Health Organization to declare a pandemic on 12 March 2020. To date, the world has paid a high toll in this pandemic in terms of human lives lost, economic repercussions and increased poverty. In this review, we provide information regarding the epidemiology, serological and molecular diagnosis, origin of SARS-CoV-2 and its ability to infect human cells, and safety issues. Then we focus on the available therapies to fight COVID-19, the development of vaccines, the role of artificial intelligence in the management of the pandemic and limiting the spread of the virus, the impact of the COVID-19 epidemic on our lifestyle, and preparation for a possible second wave.
Background: In late December 2019, Chinese health authorities reported an outbreak of pneumonia of unknown origin in Wuhan, Hubei Province. Summary: A few days later, the genome of a novel coronavirus was released (http://virological.org/t/novel-2019-coronavirus-genome/319; Wuhan-Hu-1, GenBank accession No. MN908947) and made publicly available to the scientific community. This novel coronavirus was provisionally named 2019-nCoV, now SARS-CoV-2 according to the Coronavirus Study Group of the International Committee on Taxonomy of Viruses. SARS-CoV-2 belongs to the Coronaviridae family, Betacoronavirus genus, subgenus Sarbecovirus. Since its discovery, the virus has spread globally, causing thousands of deaths and having an enormous impact on our health systems and economies. In this review, we summarize the current knowledge about the epidemiology, phylogenesis, homology modeling, and molecular diagnostics of SARS-CoV-2. Key Messages: Phylogenetic analysis is essential to understand viral evolution, whereas homology modeling is important for vaccine strategies and therapies. Highly sensitive and specific diagnostic assays are key to case identification, contact tracing, identification of the animal source, and implementation of control measures.
Two missense mutations were uncovered in the IIGT1A6 (HLUG PI) cDNA which codes for a human phenol-metabolizing UDP-glucuronosyltransferase. The mutant and a wild- type IJGT1A6 cDNAs were isolated from a custom synthesized human liver λ Zap cDNA library. Both an A to G transition at nucleotide 541 (T181 A) and an A to C transversion at nucleotide 552 (R184S) occurred in exon 1 of the UGT1A6 (UGT1F) gene at the UGT1 locus. The two mutations on a single allele created a heterozygous genotype. Newly created Bsml and BsoFl sites at the T181 A and Rl 84S locations, respectively, were confirmed by endonuclease treatment of PCR-generated DNA using the donor-liver genomic DNA as template. Screens with endonuclease treatment showed that 33/98 DNA samples were heterozygous with both mutations on one allele. One other individual also carried the Rl 84S mutation on the second allele. Wild-type UGT1A6 generated a broad plateau of activity from pH 5.0 to pH 8.0 with certain experimental phenols, while activity was 1.3-2.5-fold higher at pH 6.4 than at pH 7.2 for others. UGT1A*2 (181 A+ and 184S+) metabolized 4-nitrophenol, 4-tert-butylphenol, 3-ethylphenoI/4-ethylphenol, 4-hydroxycoumarin, butylated hydroxy anisole and butylated hydroxy toluene, with the pH 6.4 preference, at only 27-75% of the rate of the wild-type isozyme whereas 1-naphthol, 3-iodophenol, 7-hydroxycoumarin, and 7-hydroxy-4-methylcoumarin were metabolized at essentially the normal level. Furthermore, UGT1 A6*2 metabolized 3-O-methyl-dopa and methyl salicylate at 41-74% of that of the wild-type, and a series of P-blockers at 28-69% of the normal level. This evidence suggests that the UGT1A6 enzyme activity is affected by different amino acids depending upon the substrate selection.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has prompted the scientific community and the pharmaceutical companies to put maximum efforts into developing vaccines to contain the spread of this disease. Presently, many vaccines have been developed and authorized for use in human beings in different countries. In particular, in Europe to date, the Pfizer-BioNTech, Moderna, AstraZeneca and Janssen COVID-19 vaccines have been authorized. All of them are based on a version of the spike (S) glycoprotein characterized at the beginning of the pandemic. However, they differ by their level of efficacy against COVID-19. SARS-COV-2, like other RNA viruses, mutates continually. Genome sequencing analysis shows a nucleotide substitution rate of about 1 × 10−3 substitutions per year that leads to the emergence of variants through point mutations, insertions, deletions and recombination. There is concern about the ability of the current vaccines to protect against emerging viral variants. Mutations in the S-glycoprotein may affect transmission dynamics and the risk of immune escape. In this review, we address the different technological platforms in use for developing COVID-19 vaccines, the impact of emerging viral variants on virus transmission, hospitalization, and response to current vaccines, as well as rare but important adverse reactions to them. Finally, different methods for measuring antibody response to the vaccines, including the importance of using the WHO International Standard to calibrate immunoassays accurately to an arbitrary unit, to reduce interlaboratory variation and to create a common language for reporting results, are reported.