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Recent advances in antiviral effects of probiotics: potential mechanism study in prevention and treatment of SARS-CoV-2.

ABSTRACT: SARS-CoV-2 is responsible for coronavirus disease 2019 (COVID-19), progressively extended worldwide countries on an epidemic scale. Along with all the drug treatments suggested to date, currently, there are no approved management protocols and treatment regimens for SARS-CoV-2. The unavailability of optimal medication and effective vaccines against SARS-CoV-2 indicates the requirement for alternative therapies. Probiotics are living organisms that deliberate beneficial effects on the host when used sufficiently and in adequate amounts, and fermented food is their rich source. Probiotics affect viruses by antiviral mechanisms and reduce diarrhea and respiratory tract infection. At this point, we comprehensively evaluated the antiviral effects of probiotics and their mechanism with a particular focus on SARS-CoV-2. In this review, we suggested the conceptual and potential mechanisms of probiotics by which they could exhibit antiviral properties against SARS-CoV-2, according to the previous evidence concerning the mechanism of antiviral effects of probiotics. This study reviewed recent studies that speculate about the role of probiotics in the prevention of the SARS-CoV-2-induced cytokine storm through the mechanisms such as induction of anti-inflammatory cytokines (IL-10), downregulation of pro-inflammatory cytokines (TNF-α, IL-2, IL-6), inhibition of JAK signaling pathway, and act as HDAC inhibitor. Also, the recent clinical trials and their outcome have been reviewed.

Supplementary information

The online version contains supplementary material available at 10.1007/s11756-022-01147-y.

SUBMITTER: Montazeri-Najafabady N

PROVIDER: S-EPMC9244507 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Coronaviruses have caused multiple epidemics in the past two decades, in addition to the current COVID-19 pandemic that is severely damaging global health and the economy. Coronaviruses employ between twenty and thirty proteins to carry out their viral replication cycle including infection, immune evasion, and replication. Among these, nonstructural protein 16 (Nsp16), a 2'-O-methyltransferase, plays an essential role in immune evasion. Nsp16 achieves this by mimicking its human homolog, CMTr1, which methylates mRNA to enhance translation efficiency and distinguish self from other. Unlike human CMTr1, Nsp16 requires a binding partner, Nsp10, to activate its enzymatic activity. The requirement of this binding partner presents two questions that we investigate in this manuscript. First, how does Nsp10 activate Nsp16? While experimentally-derived structures of the active Nsp16/Nsp10 complex exist, structures of inactive, monomeric Nsp16 have yet to be solved. Therefore, it is unclear how Nsp10 activates Nsp16. Using over one millisecond of molecular dynamics simulations of both Nsp16 and its complex with Nsp10, we investigate how the presence of Nsp10 shifts Nsp16's conformational ensemble in order to activate it. Second, guided by this activation mechanism and Markov state models (MSMs), we investigate if Nsp16 adopts inactive structures with cryptic pockets that, if targeted with a small molecule, could inhibit Nsp16 by stabilizing its inactive state. After identifying such a pocket in SARS-CoV-2 Nsp16, we show that this cryptic pocket also opens in SARS-CoV-1 and MERS, but not in human CMTr1. Therefore, it may be possible to develop pan-coronavirus antivirals that target this cryptic pocket. Coronaviruses are a major threat to human health. These viruses employ molecular machines, called proteins, to infect host cells and replicate. Characterizing the structure and dynamics of these proteins could provide a basis for designing small molecule antivirals. In this work, we use computer simulations to understand the moving parts of an essential SARS-CoV-2 protein, understand how a binding partner turns it on and off, and identify a novel pocket that antivirals could target to shut this protein off. The pocket is also present in other coronaviruses but not in the related human protein, so it could be a valuable target for pan-coronavirus antivirals.

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Recent advances in antiviral effects of probiotics: potential mechanism study in prevention and treatment of SARS-CoV-2.

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