It is now established that a protein can switch between multiple conformations to enable altered functions. Several pathogens including SARS COV2 utilize context-dependent conformational switches of particular proteins to invade host membrane to establish infections. In this perspective, we first discuss the understanding of the conformational switch of a protein towards the productive infections as a dark side of nature. Next, the unexplored binary combination of the sequences of SARS COV2 spike protein and the similarity with diverse pathogen derived proteins have been discussed to obtain novel molecular insights into the process of infection. U nderstanding the entry process of pathogens (including virus, bacteria, and other parasites) inside hosts is crucial in order to design the strategy of resistance. In this context, it is well known that many pathogenic systems utilize specific protein molecules, which play crucial roles in the internalization process of the pathogens. These pathogen-derived proteins may not show activity in their native states, while undergo inactive to active state conformational transitions when introduced to external stimuli, including pH, surface receptor binding, post-translational modifications, and mutations. This change in conformation from one state to another of potentially varying functions is sometimes referred as conformational switch 1. The environment-sensitive conformational change of a protein is critical determinant of its biological function 2. In 1959, a talk by Dr. Richard P. Feynman entitled, "There's plenty of room at the bottom", tried to attract the scientific community's focus toward the possibilities of nanotechnologies. In this talk, he was motivated by some biological systems which play their distinct roles in different contexts and these functions are separated from one another by a small energy barrier. Proteins are the most common examples of these systems that can switch their functions with the change of environmental conditions. Protein designers are now trying to create protein sequences that can adopt numerous specific conformations and to control the relative stability of these states, advancing the molecular machines envisioned by Dr. Feynman. Conformational switches in bacterial and parasite proteins Conformational switches that occur naturally can be of different forms. Some exhibit a change from a disordered to an ordered state, whereby the transition would encompass an entire protein

, expressed in all stages of leishmanial life cycle, is considered a potential candidate for leishmaniasis vaccine. KMP-11 is found on the membrane surface of the parasite. Although the biological function of KMP-11 is unknown, we hypothesize from its sequence analysis that it may interact with the macrophage membrane and may influence the entry process of the parasite into the host cell. To validate this hypothesis, we have investigated the interaction of KMP-11 with unilamellar anionic phospholipid vesicles and explored its pore-forming activity. The decrease in negative ζpotential of the vesicles and reduction in the fluorescence intensity of membrane-bound dye DiI C-18 suggest a strong association of KMP-11 with the membrane. The fluorescence leakage experiment as well as phase contrast microscopy shows direct evidence of KMP-11-induced pore formation in an anionic membrane. Incorporation of cholesterol into the membrane has been found to inhibit pore formation induced by KMP-11, suggesting an important role of cholesterol in leishmaniasis. Interestingly, vesicles containing only neutral phospholipid do not exhibit any tendency toward pore formation.

The recent outbreak of Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) from Wuhan, China, was caused by a single-stranded RNA virus which has kept the entire world stranded. The outbreak was first diagnosed with respiratory illness, but recent findings of acute necrotizing hemorrhage of brain, brain encephalopathy, and the presence of the virus in the cerebrospinal fluid (CSF) have unveiled its neuroinvasivness. Various clinical features related to the central nervous system (CNS) and peripheral nervous system (PNS) due to COVID-19 infection are now identified. We demonstrate here an apparent similarity in neurological disorders of COVID-19 with CNS tuberculosis, which suggests that some anti-tubercular drugs may be used as therapeutic agents against COVID-19 infection.

In cell lineage commitment decisions, a gene regulatory network (GRN) consisting of a limited number of transcription factors forms the regulatory pivot. Myeloid lineage dendritic cells or DCs are specialized cells having the antigen‐presenting ability and are of immense importance in immune surveillance. In this report, we analyze the GRN that governs the lineage commitment of Common DC Progenitor (CDP) cells to conventional dendritic cells (cDC) and plasmacytoid dendritic cells (pDC). We have analyzed the quantitative behavior of the master regulatory circuit of CDP that governs the lineage commitment. Simulations showed that the GRN displays a bi‐stable behavior within a range of parameter values. Several transcription factors, PU.1, IRF8, Flt3, and Stat3, whose concentrations vary significantly in the two steady states, appear to be the key players. We hypothesize that the two stable steady states are precursors of cDC and pDC, and the variation of concentration of these key transcription factors in the two states may be responsible for early events in lineage commitment.