Coronavirus: a biochemical approach to the disease
Coronavirus

Author: Gianpiero Pescarmona
Date: 13/03/2020

Description

Aim of this page is to identify the molecular bases of Cov-2 interaction with the host

Risk Factors

COVID-19 and Italy: what next? 13/03/20

The mean age of those who died in Italy was 81 years and more than two-thirds of these patients had diabetes, cardiovascular diseases, or cancer, or were former smokers. It is, therefore, true that these patients had underlying health conditions, but it is also worth noting that they had acute respiratory distress syndrome (ARDS) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia, needed respiratory support, and would not have died otherwise.

All the conditions associated with a worse prognosis are associated with a higher level of cortisol, as aging does

aging and cortisol.
aging and cortisol

Aging

Cortisol and DHEA

Impact of psychological and endocrine factors on cytokine production of healthy elderly people. 2003

Cortisol levels were increased whereas DHEA levels were significantly reduced in the elderly.

Glutathione (GSH)

As GSH decreases with age, diseases, and environmental factors we can assume that the increased sensitivity to the Coronavirus infection can also depend on low GSH.

aging and glutathione
aging and glutathione

Sex differences

Out of 10 infected and heavily symptomatic, 7 are males and 3 are females; in elder people, the ratio is 8 to 2. The same on dead people.

Air pollution
Coronavirus: Is There Something in the Air? 07/03/2020

The three epicentres of the coronavirus epidemic, Wuhan, China; Qom, Iran and Lombardy, Italy do share something in common: extremely high levels of air pollution.

Air pollution may reduce body GSH, and low level of GSH are associated with different symptoms, including insulin resistance and diabetes, one of the death risk factors in infected patients.

Protective effect of GSH

As it is possible to modulate GSH level by dietary supply (Body GSH Upregulation) its increase can be a sound approach to prevention or even treatment of COVID19 infections

Direct anti-Viral activity

Antiviral Compounds Against Nucleocapsid Protein of Porcine Epidemic Diarrhea Virus, 2017

Antiviral activity in PEDV-infected Vero cells demonstrated that the effective concentration of trichlormethiazide, D-(+) biotin, and glutathione in inhibiting PEDV replication were 0.094, 0.094 and 1.5 mg/mL.

Acid Vesicles

Chloroquine

Pescarmona G Chloroquine

In vitro chloroquine was able to inhibit HIV replication by alkalinization of lymphocytes lysosomes.

NF-κB

aging+and+cortisol Coronavirus and NF-kB

Inhibition of NF-κB-mediated inflammation in severe acute respiratory syndrome coronavirus-infected mice increases survival. 2014

Most important, treatment with drugs that inhibited NF-κB activation led to a reduction in inflammation and lung pathology in both SARS-CoV-infected cultured cells and mice and significantly increased mouse survival after SARS-CoV infection.

Nucleocapsid protein of SARS-CoV activates interleukin-6 expression through cellular transcription factor NF-kappaB. 2007

Oxidative stress and regulation of glutathione in lung inflammation.2000

... the role of glutathione in oxidant-mediated susceptibility/tolerance, gamma-glutamylcysteine synthetase genetic susceptibility and the potential therapeutic role of glutathione and its precursors in protecting against lung oxidant stress, inflammation, and injury.

nf-kb and coronavirus

Therapy

As Glutathione (GSH) decreases with age, diseases, and environmental factors we can assume that the increased sensitivity to the Coronavirus infection depends on low GSH.

aging and glutathione

Other pathologies with low GSH

nf-kb and cortisol

nf-kb and glutathione

Il6 and glutathione

i-kb+and+glutathione

Thiol Regulation of the Production of TNF-alpha, IL-6 and IL-8 by Human Alveolar Macrophages 1999

Risk FactorsDHEACortisolGSHVit D
Agelowhighlowlow
Diabeteslowhighlowlow
Hypertensionlowhighlowlow
Diuretics-high--
Drugs--lowlow
Air Pollution--lowlow

Conflicting results:

The membrane protein of SARS-CoV suppresses NF-kappaB activation. 2007

Comments
2020-03-23T10:19:59 - Annamaria Vernone

http://draco.cs.wpi.edu/wuhan/korkin_wuhan_preprint.pdf

"Searching against UniProt database [52] resulted in matches for the polyprotein (wORF1ab vedere https://www.preprints.org/manuscript/202002.0372/v1/download), all four
structural proteins (wS, wE, wM, and wN), and six ORFs (wORF3a, wORF6, wORF7a, wORF7b,
wORF8, and wORF10) also referred to as accessory proteins"

"There is an important interaction between the SARS spike protein (S) and the host angiotensin-converting
enzyme 2 (ACE2), as it is associated with cross-species and human-to-human transmissions."

Da https://www.preprints.org/manuscript/202002.0372/v1/download

"The recently sequenced genomes of SARS-CoV-2 strains combined with the comparative analysis of the
SARS genome organization and transcription allowed us to construct a tentative list of gene products
(Sawicki, S.G., D.L. Sawicki, and S.G. Siddell, A contemporary view of coronavirus transcription.
Journal of virology, 2007. 81(1): p. 20-29). It has been suggested that SARS-CoV-2 has 16 predicted non-structural proteins (referred to as
wNsp1-wNsp16) constituting a polyprotein (wORF1ab), followed by (at least) 13 downstream open
reading frames (ORFs): Surface, ORF3a, ORF3b, Envelope, Membrane, ORF6, ORF7a, ORF7b, ORF8,
Nucleocapsid, ORF9a, ORF9b, and ORF10 that we refer in this work as wS, wORF3a, wORF3b, wE,
wM, wORF6, wORF7a, wORF7b, wORF8, wN, wORF9a, wORF9b, and wORF10, respectively. The
three viral species whose proteins shared the highest similarity were consistently the same: human SARS
(SARS-CoV), bat coronavirus (BtCoV), as well as another bat betacoronavirus (BtRf-BetaCoV)."

wS, surface glycoprotein Ysurface glycoprotein [Severe acute respiratory syndrome coronavirus 2]
https://www.ncbi.nlm.nih.gov/protein/1796318598

(https://www.uniprot.org/uniprot/Q9BYF1)
RefSeq Link NM_021804; NP_068576; UniProt#: Q9BYF1; GeneID: 59272;

2020-03-20T14:22:06 - Annamaria Vernone

SARS-CoV-2 https://www.labome.com/method/Wuhan-2019-Novel-Coronavirus-SARS-CoV-2.html

Mary Johnson (han at labome dot com)
Synatom Research, Princeton, New Jersey, United States
DOI//dx.doi.org/10.13070/mm.en.10.2867
Datelast modified : 2020-03-18; original version : 2020-01-23
Cite asMATER METHODS 2020;10:2867

Abstract

The article includes discussions on Remdesivir and COVID-19 mortality rate; important articles; important information websites; SARS-CoV-2 genome information and research reagents / instruments. The article is updated daily.

SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor (https://www.ncbi.nlm.nih.gov/pubmed/32142651).

https://www.ncbi.nlm.nih.gov/labs/virus/vssi/#/virus?SeqType_s=Protein&VirusLineage_ss=SARS-CoV-2,%20taxid:2697049

2020-03-17T17:23:23 - Annamaria Vernone

Nature Medicine, Published: 16 March 2020
Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19

As pro-inflammatory cytokines and chemokines are predictive of severe clinical outcomes for influenza6, we quantified 17 pro-inflammatory cytokines and chemokines in plasma 16 03 2020

"This patient did not experience complications of respiratory failure or acute respiratory distress syndrome, did not require supplemental oxygenation, and was discharged within a week of hospitalization, consistent with non-severe but symptomatic disease."

"our study indicates that robust multi-factorial immune responses can be elicited to the newly emerged virus SARS-CoV-2 and, similar to the avian H7N9 disease8, early adaptive immune responses might correlate with better clinical outcomes"

figure 3

glutathione and RANTES


[Correlationship between chemokines and oxidative stress in chronic hepatitis B]. 2012

Abstract »
Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of IFN-gamma-inducible protein-10 (IP-10) and regulated on activation normal T-cell-expressed and secreted (Rantes) and oxidative stress parameters (glutathione, GSH; glutathione disulfide, GSSG).

Blood Group A worse than 0?

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