Thread by @__ice9

"Of note, these viruses do not appear to cause disease in bats"--
- Nipah virus
- Hendra virus
- SARS-CoV
- SARS-CoV-2
- MERS-CoV
- Ebola
- Marburg

"ability of bats to harbor these viruses with no observed clinical consequence"

frontiersin.org/articles/10.33…

One mechanism for bat immunity-- enhanced interferon-alpha response.

This is interesting, as inhaled nebulized interferon alpha-2b and the interferon inducer umifenovir have both shown excellent results in treating COVID-19 in Chinese trials.

newatlas.com/science/why-de…

Bats also apparently have a lessened degree of inflammation compared to most mammals, which facilitates their heightened interferon response.

Treatment with anti-inflammatories has also proven quite helpful in responding to COVID-19.

discovermagazine.com/health/why-bat…

Bat natural killer (NK) cell receptors and type I major histocompatibility class (MHC) proteins are more complex than in humans, may better recognize infected cells.

Type I interferon genes exist in greater variety (22 variants vs. only 1 in humans).

immunology.sciencemag.org/content/3/24/e…

Further, bats have more potent interferon-induced transmembrane proteins (IFITMs), endosomal restriction factors that block the pH-driven fusion of enveloped viruses with endosome membranes.

Chloroquine and niclosamide also inhibit endosome fusion.

ncbi.nlm.nih.gov/pmc/articles/P…

Bats have slightly more parallel paths for detecting dsRNA intermediates inside cells and triggering apoptosis:
mbio.asm.org/content/10/6/e…

Meanwhile, ciclesonide inhibits viral protein NSP15, which mediates evasion of dsRNA sensors and limits e.g. macrophage apoptosis.

RNase L actively destroys RNA in the cell (cellular and viral).

Although this is a stronger effect, it vaguely resembles the role of ribonucleoside analogues (remdesivir, ribavirin) in _blocking_ RNA replication.

Favipiravir and indomethacin also inhibit viral RNA replication.

Nitazoxanide is also an interferon inducer, as is tilorone.

Interestingly, both do cause hyperthermia, particularly in high doses (nitazoxanide is also a weak mitochondrial uncoupler, though this is of limited clinical importance).

Fruit bat cells (incl. lung) have slower furin enzymes than human lung cells.

The furin cleavage site of SARS-CoV-2 Spike protein triggers viral fusion protein deployment while Spike is bound to ACE-2.

Furin inhibitors have been proposed for COVID-19.

ncbi.nlm.nih.gov/pmc/articles/P…

SARS-CoV-2 is proposed to have a more accessible furin cleavage site and bind to the human ACE-2 receptor more tightly than SARS-CoV.

medicalnewstoday.com/articles/why-d…

The SARS-CoV Spike protein binds less efficiently to ACE-2 receptors from various bat species than to human ACE-2.

I am not certain whether this is likewise true for SARS-CoV-2.

ACE inhibitors have been proposed for acute treatment of COVID-19.

ncbi.nlm.nih.gov/pmc/articles/P…

The SARS-CoV-2 Spike RBD may have come from a recombination event with a pangolin coronavirus regardless, so this aspect is perhaps less relevant to bats specifically.

theconversation.com/coronavirus-or…

Another overview article on the speculated origins of SARS-CoV-2:

newyorker.com/science/elemen…

I have been unable to locate much on inhibition of viral proteases in bat cells (relevant to lopinavir and nelfinavir, though efficacy looks weak regardless).

I have been likewise unable to find information on bat cell membrane cholesterol transport (relevant to itraconazole).

Overall, though:

To fight a bat virus, drugs that make the human innate immune system behave more like a bat show the most promise.