Paxlovid and new Covid variants

[johnliston]

Has anyone seen any data on how effective Paxlovid is against the new and up and coming Covid variants?

john

[cllady01 Former Volunteer]

I don't know what new variants have arrived since your same question 26 days ago. My friends who have had COVID in the last two weeks, have found Paxlovid worked for them, so I would assume it is as viable as it has been from the start. Part of what helps it to be viable is the vaccinations with boosters while you are clear of the virus.

[johnliston]

The new variants (omicron 4.6 among others) are not yet dominant. 5.0 is the dominant strain now, Paxlovid and Evusheld work against 5.0, but Evusheld is not effective against 4.6, and I wondered if Paxlovid is still considered effective against 4.6. Your friends probably had 5.0. The vaccines are not effective for me.

john

[bkoffman CLL CURE Hero in reply to johnliston]

Seems to me that mutations in the spike proteins should not diminish Paxlovid's efficacy as it works on the interior reproduction and so far that seems to be the case.

[johnliston in reply to bkoffman]

Thanks Brian, that's good to know.

john

[gardening-girl]

To follow up on Dr. Koffman's comments about the target of Paxlovid, mutations in circulating SARS-CoV-2 strains that confer resistance to Paxlovid have been found, but I haven't seen any data correlating Paxlovid resistance with any particular SARS-CoV-2 strain. The reference below which is a preprint, not yet peer reviewed, is an extensive study of mutations in the SARS-CoV-2 protease enzyme that is the target of nirmatrelvir, the active ingredient in Paxlovid. I could find no reference to from which viral strains the 100 protease mutants were identified, although considering the extensive research that was done on these mutants, it is unlikely the genomic sequences would have been from the most recent VOCs.

Extracted from the paper:

Paxlovid resistant SARS-CoV-2 viruses with mutations in the main protease have been identified from clinical isolates. In this study, we identified 100 naturally occurring Mpro mutations located at the nirmatrelvir binding site, among which 20 mutants, including S144M/F/A/G/Y, M165T, E166G, H172Q/F, and Q192T/S/L/A/I/P/H/V/W/C/F, showed comparable enzymatic activity to the wild-type (kcat/Km 10-fold increase). 

Collectively, our results have several implications. First, all 100 Mpro mutants characterized in this study are naturally occurring SARS-CoV-2 Mpro polymorphisms that could potentially affect the efficacy of Paxlovid, and continuous prescription of Paxlovid might likely increase the frequency of these pre-existing drug resistance mutants. Second, S144, M165, E166, H172, and Q192 appear to be hot spots for nirmatrelvir resistance and need to be closely monitored among circulating viruses. Mutations at these residues are most likely to maintain the enzymatic activity while causing a significant drug resistance. 

Naturally occurring mutations of SARS-CoV-2 main protease confer drug resistance to nirmatrelvir Preprint Server  bioRxiv

biorxiv.org/content/10.1101... 

[tesoro5858]

I don't know about Paxlovid and appreciate reading the replies that you have received. I read a recent posting from a member that the new variants, BQ.1 and BQ.1.1, are both completely evading Evusheld and bebtelovimab. That would leave only the antiviral treatments as options if I understand the other replies correctly.

[johnliston in reply to tesoro5858]

These are all antiviral treatments. Evusheld and bebtelovimab are monoclonal antibodies, (premade antibodies ready to attack the virus on their own). What I assume your referring to as antivirals are vaccines. Vaccines are pieces or copies of the virus that cause our immune system to produce antibodies against the virus. Unfortunately, CLL is a cancer of the immune system, so for many of us our immune systems can't respond to the stimulus and produce antibodies. So even if the vaccines are effective against these newer variants, they will not work for many of us with CLL.

john