As the COVID-19 is still growing throughout the globe, a thorough investigation into the specific immunopathology of SARS-CoV-2, its interaction with the host immune system and pathogen evasion mechanism may provide a clear picture of how the pathogen can breach the host immune defenses in elderly patients and patients with comorbid conditions. Such studies will also reveal the underlying mechanism of how children and young patients can withstand the disease better. The study of the immune defense mechanisms and the prolonged immune memory from patients population with convalescent plasma may help in designing a suitable vaccine candidate not only for the current outbreak but also for similar outbreaks in the future. The vital drug candidates, which are being tested as potential vaccines or therapeutics against COVID-19, include live attenuated vaccine, inactivated or killed vaccine, subunit vaccine, antibodies, interferon treatment, repurposing existing drugs, and nucleic acid-based vaccines. Several organizations around the world have fast-tracked the development of a COVID-19 vaccine, and some drugs already went to phase III of clinical trials. Hence, here, we have tried to take a quick glimpse of the development stages of vaccines or therapeutic approaches to treat this deadly disease.

Bacterial infections cause severe medical problems worldwide, resulting in considerable death and loss of capital. With the ever-increasing rise of antibiotic-resistant bacteria and the lack of development of new antibiotics, research on metal-based antimicrobial therapy has now gained pace. Metal ions are essential for survival, but can be highly toxic to organisms if their concentrations are not strictly controlled. Through evolution, bacteria have acquired complex metal-management systems that allow them to acquire metals that they need for survival in different challenging environments while evading metal toxicity. Metalloproteins that controls these elaborate systems in the cell, and linked to key virulence factors, are promising targets for the anti-bacterial drug development. Among several metal-sensory transcriptional regulators, the ArsR-SmtB family displays greatest diversity with several distinct metal-binding and nonmetal-binding motifs that have been characterized. These prokaryotic metolloregulatory transcriptional repressors represses the expression of operons linked to stress-inducing concentrations of metal ions by directly binding to the regulatory regions of DNA, while derepression results from direct binding of metal ions by these homodimeric proteins. Many bacteria, e.g., Mycobacterium tuberculosis, Bacillus anthracis, etc., have evolved to acquire multiple metal-sensory motifs which clearly demonstrate the importance of regulating concentrations of multiple metal ions. Here, we discussed the mechanisms of how ArsR-SmtB family regulates the intracellular bioavailability of metal ions both inside and outside of the host. Knowledge of the metal-challenges faced by bacterial pathogens and their survival strategies will enable us to develop the next generation drugs.

The ArsR-SmtB family of proteins displays the greatest diversity among the bacterial metal-binding transcriptional regulators with regard to the variety of metal ions that they can sense. In the presence of increased levels of toxic heavy metals, these proteins dissociate from their cognate DNA upon the direct binding of metal ions to the appropriate sites, designated motifs on the proteins, either at the interface of the dimers or at the intra-subunit locations. In addition to the metal-mediated regulation, some proteins were also found to control transcription via redox reactions. In the present work, we have identified several new sequence motifs and expanded the knowledge base of metal binding sites in the ArsR-SmtB family of transcriptional repressors, and characterized them in terms of the ligands to the metal, distribution among different phyla of bacteria and archaea, amino acid propensities, protein length distributions and evolutionary interrelationships. We built structural models of the motifs to show the importance of specific residues in an individual motif. The wide abundance of these motifs in sequences of bacteria and archaea indicates the importance of these regulators in combating metal-toxicity within and outside of the hosts. We also show that by using residue composition, one can distinguish the ArsR-SmtB proteins from other metalloregulatory families. In addition, we show the importance of horizontal gene transfer in microorganisms, residing in similar habitats, on the evolution of the structural motifs in the family. Knowledge of the diverse metalloregulatory systems in microorganisms could enable us to manipulate specific genes that may result in a toxic metal-free environment.

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