Replies to post #142128 on NanoViricides Inc. (NNVC)

[NewMoney]

Well good luck. I truly want to see you guys make money. I just, as you know, don’t have confidence in this being the right biotech.

[KMBJN]

Wow, something of a bombshell here in this pre-print study of 2019n-CoV genome: the S spike on the new virus (which is typically the protein used to enter a cell) is nothing like other coronaviruses. Instead it seems to have "inserts" from HIV-1 gene segments encoding gp120 and Gag. This brings up the whole idea that it was artificially created, i.e. a bioweapon that was accidentally released. We'll see if anyone else confirms this troubling conclusion:

https://www.biorxiv.org/content/10.1101/2020.01.30.927871v1

So, despite the previous paper seeing more similarity to SARS (with ACE2 cellular entry receptor) versus MERS (with DPP-IV receptor), this new virus appears to be some wacky combination of HIV (which uses CCR5 and CXCR4 to enter cells) with previous CoV like SARS.

NNVC / Diwan seems to have his work cut out for him to model a ligand based on this modified S spike protein.

"Since the S protein of 2019-nCoV shares closest ancestry with SARS GZ02, the sequence coding for spike proteins of these two viruses were compared using MultiAlin software. We found four new insertions in the protein of 2019-nCoV- “GTNGTKR” (IS1), “HKNNKS” (IS2), “GDSSSG” (IS3) and “QTNSPRRA” (IS4) (Figure 2). To our surprise, these sequence insertions were not only absent in S protein of SARS but were also not observed in any other member of the Coronaviridae family (Supplementary figure). This is startling as it is quite unlikely for a virus to have acquired such unique insertions naturally in a short duration of time. "

"Further analysis revealed that aligned sequences of HIV-1 with 2019-nCoV were derived from surface glycoprotein gp120 (amino acid sequence positions: 404-409, 462-467, 136-150) and from Gag protein (366-384 amino acid) (Table 1). Gag protein of HIV is involved in host membrane binding, packaging of the virus and for the formation of virus-like particles. Gp120 plays crucial role in recognizing the host cell by binding to the primary receptor CD4.This binding induces structural rearrangements in GP120, creating a high affinity binding site for a chemokine co-receptor like CXCR4 and/or CCR5."

Maybe it's time to break out the HIV-cide instead of the previous MERS-cide. Wonder if Lulu and Nana are resistant to this mutant combo HIV-CoV.

Very interesting.

[KMBJN]

Diwan is making a CoVID-19-cide anyways, and will be testing it on a less virulent strain of coronavirus that also uses ACE2 to infect cells. From the 10-Q:

Subsequent to the reporting period, on January 30, 2020, the Company confirmed in a press release that it has undertaken an effort to develop a treatment for the novel 2019-nCoV coronavirus outbreak that appears to have started around November-December 2019 in Wuhan, China. The new 2019-nCoV is known to be closely related to the SARS-CoV of 2002-2003 epidemic. In fact it has been shown to use the same cell surface receptor as SARS-CoV, namely ACE2. The Company determined, based on molecular modeling screening that it had in its chemicals library ligands that could bind to SARS-CoV S1 spike protein at the same position where the S1 binds to the human receptor ACE2. It is a reasonable expectation that these relatively broad-spectrum ligands would also be able to bind the S1 spike protein of the NCP coronavirus in the same fashion. The Company intends to generate nanoviricides based on these ligands and test them in our own BSL2 virology lab facility against known available human pathogen coronaviruses, including those that use ACE2 as the cellular receptor. The Company has the capacity to produce several thousand doses of the potential drug at its cGMP-capable multi-purpose manufacturing facility in Shelton, CT. If this screening produces positive results, then the Company anticipates obtaining assistance from US government and international agencies for further testing and potential exploratory clinical use to combat the epidemic. The Company does not at present have any active collaborations with US or international agencies for this purpose. Even if the Company can develop a potential drug candidate, significant support and participation from US and international agencies would be required to make it available to patients, including for taking it through exploratory clinical trials. The outbreak was declared a global emergency by the WHO on the same date, January, 30th, 2020.

[KMBJN]

Interesting that others are trying to make similar artificial viral traps against SARS-CoV-2, using ACE2 receptor as a "decoy" or mimic, just like what Diwan/Theracour/NNVC is doing:

https://finance.yahoo.com/news/sorrento-develops-sti-4398-covidtrap-110010134.html

STI-4398 is a proprietary ACE2 (angiotensin-converting enzyme 2)-Fc fusion protein (COVIDTRAP). The STI-4398 protein binds to the S1 domain of the spike protein, which is expected to block the spike protein of the SARS-CoV-2 virus to bind the ACE2 receptors present on the target respiratory epithelial cells. Without the ability to penetrate target cells, the SARS-CoV-2 virus cannot replicate and spread itself. By interfering with the viral infection cycle, STI-4398 might be the most effective way to prevent an infection to progress to a fully advanced COVID-19 disease. This approach could be ideal in generating passive immunity and shielding at-risk populations, including healthcare providers, the elderly population or patients with compromised immune systems, from developing the COVID-19 disease after viral exposure.

Hard to say if their COVIDTRAP will destroy the virus or not.