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HGNC Genes

SARS-CoV-2 proteins

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    Beneficial effects of a mouthwash containing an antiviral phthalocyanine derivative on the length of hospital stay for COVID-19 MESHD

    Authors: Paulo Sérgio da Silva Santos; Bernardo da Fonseca Orcina; Rafael Rahal Guaragna Machado; Fabiano Vieira Vilhena; Lucas Marques da Costa Alves; Mariana Schutzer Ragghianti Zangrando; Rodrigo Cardoso de Oliveira; Mariana Quirino Silveira Soares; Andréa Name Colado Simão; Emilene Cristine Izu Nakamura Pietro; Juliana Pescinelli Garcia Kuroda; Ivanilda Aparecida de Almeida Benjamim; Danielle Bastos Araujo; Sérgio Hiroshi Toma; Lourival Flor; Koiti Araki; Edison Luiz Durigon

    doi:10.21203/rs.3.rs-330173/v1 Date: 2021-03-14 Source: ResearchSquare

    Background: The risk of contamination and dissemination by SARS-CoV-2 has a strong link with nasal, oral and pharyngeal cavities. Recently, our research group observed the promising performance of an anionic phthalocyanine derivative (APD) used in a mouthwash protocol without photoexcitation; this protocol improved the general clinical condition of patients infected with SARS-CoV-2. Methods: The present two-arm study evaluated in vitro the antiviral activity and cytotoxicity of APD MESHD. Additionally, a triple-blind randomized controlled trial was conducted with 41 hospitalized patients who tested positive for COVID-19 MESHD. All the included patients received World Health Organization standard care hospital treatment (non-intensive care) plus active mouthwash (experimental group AM/n=20) or nonactive mouthwash (control group NAM HGNC/n=21). The adjunct mouthwash intervention protocol used in both groups consisted one-minute gargling/rinsing / 5 times/day until hospital discharge. Groups were compared considering age, number of comorbidities, duration of symptoms prior admission and length of hospital stay (LOS). The associations between group and sex, age range, presence of comorbidities, admission to Intensive care unit (ICU) and death MESHD were also evaluated. Results: The in vitro evaluation demonstrated that APD compound was highly effective for reduction of SARS-CoV-2 MESHD viral load in the 1.0 mg/mL (99.96%) to 0.125 mg/mL (92.65%) range without causing cytotoxicity MESHD. Regarding the clinical trial, the median LOS of the AM group was significantly shortened (4 days) compared with that of the NAM HGNC group (7 days) (p=0.0314). Additionally, gargling/rinsing with APD was very helpful in reducing the severity of symptoms (no ICU care was needed) compared to not gargling/rinsing with APD (28.6% of the patients in the NAM HGNC group needed ICU care, and 50% of this ICU subgroup passed way, p=0.0207). Conclusions: This study indicated that the mechanical action of the protocol involving mouthwash containing a compound with antiviral effects against SARS-CoV-2 may reduce the symptoms of the patients and the spread of infection. The use of APD in a mouthwash as an adjuvant the hospital COVID-19 MESHD treatment presented no contraindication and reduced the hospital stay period. Trial Registration: The clinical study was registered at REBEC - Brazilian Clinical Trial Register (RBR-58ftdj).

    Coronavirus Infection and PARP HGNC Expression Dysregulate the NAD Metabolome: A Potentially Actionable Component of Innate Immunity

    Authors: Collin D Heer; Daniel J Sanderson; Lynden S Voth; Yousef M.O. Alhammad; Mark S Schmidt; Samuel A.J. Trammell; Stanley Perlman; Michael S Cohen; Anthony R. Fehr; Charles Brenner

    doi:10.1101/2020.04.17.047480 Date: 2020-04-18 Source: bioRxiv

    ABSTRACTInnate immune responses are critical to control of viruses. Coronaviruses (CoVs) are positive strand RNA viruses with double-stranded RNA replication intermediates that are recognized by the innate immune system. Upon recognition, infected cells secrete interferon, which induces a set of interferon-stimulated genes that inhibit viral replication. Here we show that SARS-CoV-2 infection strikingly dysregulates MESHD SARS-CoV-2 infection strikingly dysregulates MESHD the set of genes involved in consumption and biosynthesis of nicotinamide adenine dinucleotide (NAD). Highly induced genes include those encoding noncanonical poly(ADP-ribose) polymerase ( PARP HGNC) family members known to function as mono ADP-ribosyltransferases but not known to deplete cellular NAD and genes encoding enzymes for salvage NAD synthesis from nicotinamide ( NAM HGNC) and nicotinamide riboside (NR). We demonstrate that overexpression of PARP10 HGNC is sufficient to depress NAD levels and that the enzymatic activities of PARP10 HGNC, PARP12 HGNC and PARP14 HGNC are limited by and can be enhanced by pharmacological activation of NAM HGNC salvage. We further showed that infection with the β-coronavirus murine hepatitis virus MESHD (MHV) induces a severe attack on host cell NAD+ and NADP+. Finally we show that NAMPT HGNC activation, NAM HGNC and NR dramatically decrease replication in a MHV infection MESHD model that is sensitive to PARP HGNC activity. The data show that the antiviral activities of noncanonical PARP HGNC isozyme activities are limited by their own consumption of cellular NAD and that nutritional and pharmacological interventions to enhance NAD-based defenses may boost innate immunity.Competing Interest StatementCB is chief scientific adviser of ChromaDex and owns shares of ChromaDex stock. CB, SAJT, SP and ARF MESHD applied for a patent on uses of NAD boosting compounds to protect against CoVs. Others declare no competing interests.View Full Text

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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