SARS-CoV-2 Coronavirus (COVID-19)

Trust the $cientists…..

 

i do, wear one whenever i'm inside with others

 

I do not think that masks hurt, but I’m thinking that perhaps they are not the single most effective way to fight covid.

Of course…..I’m neither a $cientist nor a scientist.
People wonder at the skepticism…….

 

too bad, i had hoped ivermectin would prove out in further studies

 

the problem is, everyone has to wear one, and properly. they are more effective at preventing spread than protecting from, unless n95

 

talking to my doc yesterday, he said what they are seeing is people becoming complacent and letting their guard down, including masks, hand washing, distancing, and indoor gatherings.

 

Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents | Communications Biology

Emerging outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is a major threat to public health. The morbidity is increasing due to lack of SARS-CoV-2 specific drugs. Herein, we have identified potential drugs that target the 3-chymotrypsin like protease (3CLpro), the main protease that is pivotal for the replication of SARS-CoV-2. Computational molecular modeling was used to screen 3987 FDA approved drugs, and 47 drugs were selected to study their inhibitory effects on SARS-CoV-2 specific 3CLpro enzyme in vitro. Our results indicate that boceprevir, ombitasvir, paritaprevir, tipranavir, ivermectin, and micafungin exhibited inhibitory effect towards 3CLpro enzymatic activity. The 100 ns molecular dynamics simulation studies showed that ivermectin may require homodimeric form of 3CLpro enzyme for its inhibitory activity. In summary, these molecules could be useful to develop highly specific therapeutically viable drugs to inhibit the SARS-CoV-2 replication either alone or in combination with drugs specific for other SARS-CoV-2 viral targets.

 

My institution's liberry has it. They did the molecular dynamics with a timestep of four femtoseconds, so when they see an interaction lasting a µs, that baby pretty much stayed put for a quarter of a billion timesteps. That was for the interaction with ACE2, which they considered promising. By comparison, when they simulated its interactions with the two proteases, two simulations "lead to the release of IVE from the binding pocket after ca. 80 (i.e., really early stage) and 650 ns, although in the starting geometry the disaccharide moiety was in contact with the dyad. After the release, the drug interacts persistently with the external surface of 3CLpro(Fig. S7A, ESI†) instead, thanks to its flexible and large contact area."

They report that earlier authors had also noted the quick (85 ns) diffusion out, but had chalked that up to simulating the 3CLpro monomer. They had then run some simulations up to 100 ns in length using the 3CLpro dimer and not observed the diffusion out. This present paper's authors "conclude that extensive MD simulations are crucial to properly sample the instability of IVE inside the catalytic pocket and that short (nanosecond time scale) MD simulations, such as the ones already reported, could overestimate the stability of the IVE/3CLpro interaction."

Or as a starting point for drug design: "we have evidenced the establishment of favorable and rather persistent interactions with the human ACE2 receptor. In some cases, these interactions have been shown to take place at the interface used by the viral RBD unit to recognize ACE2, inducing a non-negligible destabilization of the complex that could point to a possible antiviral mechanism exploitable in future drug design strategies."

 

So I read:

Results reveal that the ACE2 protein and the ACE2/RBD aggregates form the most persistent interactions with ivermectin, while the binding with the remaining viral proteins is more limited and unspecific.​

Coating the target cell receptors is not as effective as antibodies that attack viral spikes still floating that also seek the cells. The antibodies generated from vaccination work on viral particles not yet attached but seeking a cell to infect.

Bob Wilson

 

I just found this vaccine "Delta variant effectiveness" chart from the Economist:
Which vaccine is the most effective against the Delta variant? | The Economist

It seems that I received the "right" vaccine, Moderna.

JeffD

 

..... unti next week's 'science' revelation.
.

 

This one has held on to the crown most of the year.

 

dang, i got phizer

 

A close second place.

JeffD

 

Whichever vaccine is an order of magnitude better than not being vaccinated.

Bob Wilson

 

Well, I've now had two shots of Pfizer with a Moderna chaser, so we'll see how that does.

 

Screen shot from a New York Times, e-mail list:



Bob Wilson