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Rajeev Chitguppi MDS Profile picture
@chitguppi
Sep 20, 2020 • 3 tweets • 2 min read • Read on X
#Chlorhexidine - a potential anti-#SARSCoV2 drug.

[1] New drug discovery is a long, costly, and rigorous scientific process.

[2] A more effective approach is to search from existing drug databases.

Link: J Physical Chemistry (June 2020)
doi.org/10.1021/acs.jp…
3] The study found that many existing drugs might be potentially potent medications against SARS-CoV-2. (SARS-CoV-2 3CL protease inhibitors)

[4] The study used validated machine learning models to screen 1553 drugs that are FDA-approved.

doi.org/10.1021/acs.jp…
[5] See the summary of the Top 20 Potential Anti-SARS-CoV-2 Drugs - #CHLORHEXIDINE at 11.

Link: J Physical Chemistry (June 2020)
doi.org/10.1021/acs.jp…

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More from @chitguppi

Rajeev Chitguppi MDS Profile picture
Jan 8, 2022
1/ Who gets severe COVID-19?

COVID-19 is a double-defect disease:

1. A defective early control of the virus by type I / III Interferons (IFN)

2. An impaired ability to control proinflammatory activities.

Only when both these checkpoints fail will critical disease develop.
2/ Interferons (IFN)

SARS-CoV-2 is a poor inducer of IFN:

Triggers limited & delayed type I / III IFN responses.

On the other hand, the virus is highly sensitive to IFN treatment similar to other coronaviruses.
3/ Despite modest IFN induction, this innate antiviral response is critical for infection control. #COVID19

@SciImmunology 7 Jan 2022

science.org/doi/10.1126/sc…
Read 6 tweets
Rajeev Chitguppi MDS Profile picture
Jan 8, 2022
Neutralizing antibodies are a good indicator of protection,
- not only against severe disease
- but also (if amounts are very high) against viral replication in the mucosa (with or without symptoms), thereby reducing transmission. #COVID19

However... 1/n science.org/doi/10.1126/sc…
However, this does not mean that it is circulating antibody that is causing protection:

- Antibody in the serum does not normally diffuse (or get transported) into mucosal fluids.

- Also... (2/n)
science.org/doi/10.1126/sc…
Also, protection against superficial infection depends on

- mucosal antibodies [including immunoglobulin A (IgA)],

and possibly on

- antiviral T cells that reside within the linings of the respiratory tract. (3/n)
science.org/doi/10.1126/sc…
Read 5 tweets
Rajeev Chitguppi MDS Profile picture
Jan 4, 2022
1/ Which oral/ periodontal pathogen acts similar to viruses when it comes to suppressing host immunity?

Background:

Anatomical (mucosal/ epithelial) barriers confer antiviral immunity via interferon (IFN) production.

IFNs function like antiviral cytokines...
2/ IFNs function as antiviral cytokines and restrict viral infection, replication, and release.

Oral epithelial cells fight viral infections by inducing Type III IFNs (IFN-λ) preferentially.

Latest evidence:

Recent study PNAS, 21 Dec 2021
3/ A recent study showed that IFN production and antiviral immunity are severely compromised by one oral bacterial pathogen.

And that is Porphyromonas gingivalis (Pg).

Molecular pathways employed by Pg are strikingly parallel to those utilized by viruses for IFN suppression.
Read 4 tweets
Rajeev Chitguppi MDS Profile picture
Jan 4, 2022
1/ Delta variant was highly pathogenic due to its ability to cause cell-cell fusion & syncytia formation.

But this pathogenicity came with Terms & Conditions.

"S1/2 cleavage should be optimal for cells expressing TMPRSS2 (lower airway)"

Omicron #COVID19 story is different.
2/ Cell-cell fusion mediated by spike glycoprotein requires S1/S2 cleavage, but is also dependent on TMPRSS2 presence.

Omicron spike is relatively poorly cleaved.

Way suboptimal compared to Delta

Due to this suboptimal cleavage lower airway infection is less with Omicron.
3/ So, Omicron shows impaired entry & replication in lung cells that express TMPRSS2 (a serine protease enriched in lung alveolar type 1 & 2 cells).

This reduced cleavage is also associated with poorer cell-cell fusion and syncytia formation.

This tells us about upper airway
Read 5 tweets
Rajeev Chitguppi MDS Profile picture
Jan 3, 2022
1/ Omicron's 3 mutations (P681H, H655Y, N679K) in furin cleavage site region were initially predicted to favor its pathogenicity: cell-cell fusion & syncytia formation.

But reality is different.

Omicron's cleavage efficiency is substantially lower than Delta variant. #COVID19
2/ Omicron spike is relatively poorly cleaved.

It shows impaired entry & replication in lung cells that express TMPRSS2, a serine protease enriched in lung alveolar type 1 & 2 cells.

This reduced cleavage is also associated with poorer cell-cell fusion and syncytia formation.
3/ Cell-cell fusion mediated by spike glycoprotein requires S1/S2 cleavage, but is also dependent on TMPRSS2 presence.

Fusogenicity of Omicron spike was severely impaired despite TMPRSS2 expression, leading to marked reduction in syncytium formation compared to Delta spike.
Read 4 tweets
Rajeev Chitguppi MDS Profile picture
Jan 3, 2022
Omicron infects throat more & lungs less compared to earlier variants.

Simple strategy: As soon as you get sore throat start with Chlorhexidine (CHX) mouthwash for throat gargling

Study: 4 day CHX use eliminated #SARSCOV2 virus from oropharynx. #COVID19
All studies done on Chlorhexidine and its antiviral actions esp. against SARS-COV-2 summarized in my blog

"Chlorhexidine gluconate — the most effective antiviral mouthwash in COVID-19 pandemic"

chitguppi.medium.com/chlorhexidine-…
My earlier thread on Chlorhexidine mouthwash and its antiviral effects against SARS-COV-2

Read 5 tweets

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