Suicide deaths during the COVID-19 pandemic in the United States, by region, gender and age, March 1, 2020-June 30, 2022 (preprint)

The COVID-19 pandemic imposed substantial mental health stressors leading to concerns about an increased suicide risk. To investigate this issue, we investigated suicide mortality rates in the United States from March 1, 2020, through June 30, 2022, comparing them with data from the pre-pandemic period of January 2015 through February 2020. Suicide mortality in the United States was 3% below expected levels during the study period. However, there was an increased suicide incidence in adults ages 18–34 years. The concerns that the pandemic contributed to an overall marked increase in suicide risk is not supported by this analysis, but young adults did experience an increase.

An inimitable proprotein convertase subtilisin kexin-9 (PCSK9) cleavage site VFAQ on Spike protein along with furin cleavage site makes SARS-CoV-2 unique (preprint)

A novel coronavirus (2019-nCoV) or Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) that affects humans has been discovered in Wuhan, China, in 2019. Its genome has been sequenced, and the genetic data was quickly made public. We discovered a novel proprotein convertase subtilisin kexin-9 ( PCSK9) cleavage site in the Spike protein of the 2019-nCoV. The recent research also demonstrates that the previously found proprotein convertase 3 (PC3) or furin cleavage site, which was assumed to be unique, is already present in animal corona viruses. In this article, we suggest that the combination of the both proprotein convertase PC3 cleavage site and the PCSK9 site renders SARS-CoV-2 unique in terms of the pathogenicity, potential functional effects, and implications for the development of antiviral drugs.

Artificial Neural Network Based Study Predicting GS-441524 As Potential Inhibitor of SARS COV-2 Activator Protein Furin: A Polypharmacology Approach (preprint)

Furin, a pro-protein convertase, plays a significant role of biological scissor in bacterial, viral, and even mammalian substrates which in turn decides the fate of many viral and bacterial infections along with the numerous ailments caused by cancer, diabetes, inflammations, and neurological disorders. In the wake of the current pandemic caused by the virus SARS COV-2, furin has become the center of attraction for researchers. In the present work, we have searched for novel inhibitors against this interesting human target from FDA-approved antivirals. To enhance the selection of new inhibitors we employed Kohonen’s-artificial neural network-based self-organizing maps for ligand based virtual screening. Promising results were obtained which can help in drug repurposing and network pharmacology studies addressing the errors due to promiscuity/polypharmacology. We found 15 existing FDA antivirals having the potential to inhibit furin. Among these, six compounds have targets on other important human proteins (LDLR, FCGR1A, PCK1, TLR7, DNA and PNP) also. These 15 drugs inhibiting furin could be studied in patients having many viral infections including SARS COV-2, which is known to have many interacting motifs like NSPs, ORFs, and spike protein. We also propose two promising candidate FDA drugs GS-441524 and Grazoprevir (MK-5172) to repurpose as inhibitors of furin. The best results were observed with GS-441524.

Unravelling Vitamins as Wonder Molecules for Covid-19 Management via Structure-based Virtual Screening (preprint)

The emergence situation of coronavirus disease 2019 (COVID-19) pandemic has realised the global scientific communities to develop strategies for immediate priorities and long-term approaches for utilization of existing knowledge and resources which can be diverted to pandemic preparedness planning. Lack of proper vaccine candidate and therapeutic management has accelerated the researchers to repurpose the existing drugs with known preclinical and toxicity profiles, which can easily enter Phase 3 or 4 or can be used directly in clinical settings. We focused to justify even exploration of supplements, nutrients and vitamins to dampen the disease burden of the current pandemic may play a crucial role for its management. We have explored structure based virtual screening of 15 vitamins against non-structural (NSP3, NSP5, ORF7a, NSP12, ORF3a), structural (Spike & Hemagglutinin esterase) and host protein furin. The in silico analysis exhibited that vitamin B12, Vitamin B9, Vitamin D3 determined suitable binding while vitamin B15 manifested remarkable H-bond interactions with all targets. Vitamin B12 bestowed the lowest energies with human furin and SARS-COV-2 RNA dependent RNA polymerase. Furin mediated cleavage of the viral spike glycoprotein is directly related to enhanced virulence of SARS-CoV-2. In contrast to these, vitamin B12 showed zero affinity with SARS-CoV-2 spike protein. These upshots intimate that Vitamin B12 could be the wonder molecule to shrink the virulence by hindering the furin mediated entry of spike to host cell. These identified molecules may effectively assist in SARS-CoV-2 therapeutic management to boost the immunity by inhibiting the virus imparting relief in lung inflammation.