Effects of the SARS-CoV-2 Spike protein on in vitro aggregation of alpha synuclein- probable molecular interactions and clinical implications

There have been reports of neurodegenerative diseases including Parkinsonism, Alzheimer's disease and Creutzfeldt Jakob disease following COVID-19. The exact pathogenesis of these has not been elucidated yet though authors have proposed the possibility of the hyper-inflammatory state of COVID-19 acting as a trigger through cytokine-induced inflammatory response of brain microglia and astrocytes, as well as damage resulting from the central nervous system hypoxia of severe COVID-19, or even the direct pathogenetic actions of SARS-CoV-2 on the brain. There have also been reports of worsening of Parkinsonian symptoms, new onset movement disorders and even rapidly progressive dementia following COVID-19 vaccination using different vaccine types. The occurrence of protein-aggregation mediated neurodegenerative syndromes following both COVID-19 and vaccination led us to explore the common thread of the Spike (S) protein as a potential mediator. In the current study, we investigated the interactions of S protein of SARS-CoV-2 with α-synuclein.

Evolving Face Mask Guidance During a Pandemic and Potential Harm to Public Perception: Infodemiology Study of Sentiment and Emotion on Twitter.

BACKGROUND: Throughout the COVID-19 pandemic, US Centers for Disease Control and Prevention policies on face mask use fluctuated. Understanding how public health communications evolve around key policy decisions may inform future decisions on preventative measures by aiding the design of communication strategies (eg, wording, timing, and channel) that ensure rapid dissemination and maximize both widespread adoption and sustained adherence. OBJECTIVE: We aimed to assess how sentiment on masks evolved surrounding 2 changes to mask guidelines: (1) the recommendation for mask use on April 3, 2020, and (2) the relaxation of mask use on May 13, 2021. METHODS: We applied an interrupted time series method to US Twitter data surrounding each guideline change. Outcomes were changes in the (1) proportion of positive, negative, and neutral tweets and (2) number of words within a tweet tagged with a given emotion (eg, trust). Results were compared to COVID-19 Twitter data without mask keywords for the same period. RESULTS: There were fewer neutral mask-related tweets in 2020 (ß=-3.94 percentage points, 95% CI -4.68 to -3.21; P<.001) and 2021 (ß=-8.74, 95% CI -9.31 to -8.17; P<.001). Following the April 3 recommendation (ß=.51, 95% CI .43-.59; P<.001) and May 13 relaxation (ß=3.43, 95% CI 1.61-5.26; P<.001), the percent of negative mask-related tweets increased. The quantity of trust-related terms decreased following the policy change on April 3 (ß=-.004, 95% CI -.004 to -.003; P<.001) and May 13 (ß=-.001, 95% CI -.002 to 0; P=.008). CONCLUSIONS: The US Twitter population responded negatively and with less trust following guideline shifts related to masking, regardless of whether the guidelines recommended or relaxed mask usage. Federal agencies should ensure that changes in public health recommendations are communicated concisely and rapidly.

A comprehensive SARS-CoV-2-human protein-protein interactome reveals COVID-19 pathobiology and potential host therapeutic targets.

Studying viral-host protein-protein interactions can facilitate the discovery of therapies for viral infection. We use high-throughput yeast two-hybrid experiments and mass spectrometry to generate a comprehensive SARS-CoV-2-human protein-protein interactome network consisting of 739 high-confidence binary and co-complex interactions, validating 218 known SARS-CoV-2 host factors and revealing 361 novel ones. Our results show the highest overlap of interaction partners between published datasets and of genes differentially expressed in samples from COVID-19 patients. We identify an interaction between the viral protein ORF3a and the human transcription factor ZNF579, illustrating a direct viral impact on host transcription. We perform network-based screens of >2,900 FDA-approved or investigational drugs and identify 23 with significant network proximity to SARS-CoV-2 host factors. One of these drugs, carvedilol, shows clinical benefits for COVID-19 patients in an electronic health records analysis and antiviral properties in a human lung cell line infected with SARS-CoV-2. Our study demonstrates the value of network systems biology to understand human-virus interactions and provides hits for further research on COVID-19 therapeutics.

A 3D structural SARS-CoV-2-human interactome to explore genetic and drug perturbations.

Emergence of new viral agents is driven by evolution of interactions between viral proteins and host targets. For instance, increased infectivity of SARS-CoV-2 compared to SARS-CoV-1 arose in part through rapid evolution along the interface between the spike protein and its human receptor ACE2, leading to increased binding affinity. To facilitate broader exploration of how pathogen-host interactions might impact transmission and virulence in the ongoing COVID-19 pandemic, we performed state-of-the-art interface prediction followed by molecular docking to construct a three-dimensional structural interactome between SARS-CoV-2 and human. We additionally carried out downstream meta-analyses to investigate enrichment of sequence divergence between SARS-CoV-1 and SARS-CoV-2 or human population variants along viral-human protein-interaction interfaces, predict changes in binding affinity by these mutations/variants and further prioritize drug repurposing candidates predicted to competitively bind human targets. We believe this resource ( http://3D-SARS2.yulab.org ) will aid in development and testing of informed hypotheses for SARS-CoV-2 etiology and treatments.