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Category: Active Research
Forum: OpenPandemics - COVID-19 Project
Thread: Covid-19 - Discuss Scientific Papers |
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Thread Status: Active Total posts in this thread: 80
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Aurum
Master Cruncher The Great Basin Joined: Dec 24, 2017 Post Count: 2386 Status: Offline Project Badges: 
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Computational Design of ACE2-Based Peptide Inhibitors of SARS-CoV-2 (Han & Kral, 2020)
----------------------------------------https://pubs.acs.org/doi/10.1021/acsnano.0c02...ealert_TOC_ancac3_v14_i4# Looks like a very interesting interim therapeutic approach.   ...KRI please cancel all shadow-banning[Edit 1 times, last edit by Aurum420 at May 5, 2020 4:51:12 PM] |
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Aurum
Master Cruncher The Great Basin Joined: Dec 24, 2017 Post Count: 2386 Status: Offline Project Badges:
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Han & Kral have done some beautiful preliminary work.
----------------------------------------A negative binding energy means it's spontaneous and the more negative the stronger. In Figure 2e their control is the protease domain (PD) from ACE2 and the receptor-binding domain (RBD) of SARS-CoV-2. This represents when the spike (S) protein of the virus comes into close contact with the ACE2 receptor protein on human cells and binds. They don't come out and make definitive conclusions and I'm not sure why, maybe they didn't think the binding energy was high enough to beat their chest too hard. Inhibitor 1 is out because it changes shape and they hint it might not be neutralizing, i.e. prevent viral cell entry. Inhibitor 2 gets the closest but has the weakest binding strength. Inhibitor 3 & 4 are farther apart but have higher binding strengths. General references: https://en.wikipedia.org/wiki/Ligand_(biochemistry) http://autodock.scripps.edu/faqs-help/manual/...AutoDock4.2_UserGuide.pdf ...KRI please cancel all shadow-banning[Edit 2 times, last edit by Aurum420 at May 5, 2020 5:20:29 PM] |
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Aurum
Master Cruncher The Great Basin Joined: Dec 24, 2017 Post Count: 2386 Status: Offline Project Badges:
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What might one do to improve on the work of Han & Kral (if they aren't already doing so)??? They list the key amino acids (aa) in the:
----------------------------------------alpha-1 helix; 24(Q), 27(T), 30(D), 31(K), 34(H), 35(E), 37(E), 38(D), 41(Y), and 42(Q), alpha-2 helix; 82(M), and beta-sheet linker: 353(K), 354(G), 355(D), and 357(R). (BTW, residue is a fancy word for aa in a chain.) Take a look at the "Twenty-One Amino Acids" chart at: https://en.wikipedia.org/wiki/Amino_acid Polar uncharged side chain: Q - glutamine (Gln) T - threonine (Thr) Hydrophobic side chain: M - methionine (Met) Y - tyrosine (Tyr) Negatively charged side chains: D - aspartic acid (Asp) E - glutamic acid (Glu) Positively charged side chains: H - histidine (His) K - lysine (Lys) R - arginine (Arg) One possibility to try would be to replace a similar aa with a shorter side-chain to get closer, e.g. replace 31(K) with H. Then run the simulations again looking for shape changes and binding changes. And an infinite number of other possibilities. A perfect BOINC project (wishful thinking). ...KRI please cancel all shadow-banning |
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Jim1348
Veteran Cruncher USA Joined: Jul 13, 2009 Post Count: 1066 Status: Offline Project Badges: 
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Very interesting, but with all the proposed treatments, I wonder how they decide which ones to test? And who is the "they" anyway?
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Aurum
Master Cruncher The Great Basin Joined: Dec 24, 2017 Post Count: 2386 Status: Offline Project Badges:
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And who is the "they" anyway? They obey The Golden Rule, the guy with the gold makes the rules :-)The scientists use their best judgment to select their leading candidates and then they look for a company to sponsor clinical trials. Right now there's 1,208 trials going. Play around around with this search engine: https://clinicaltrials.gov/ct2/results?cond=C...mp;rslt=&Search=Clear ...KRI please cancel all shadow-banning[Edit 1 times, last edit by Aurum420 at May 5, 2020 6:53:27 PM] |
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Jim1348
Veteran Cruncher USA Joined: Jul 13, 2009 Post Count: 1066 Status: Offline Project Badges:
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You are well protected. We didn't see a town for 50 miles along Route 50 in Nevada. It will be our last trip for a while.
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Aurum
Master Cruncher The Great Basin Joined: Dec 24, 2017 Post Count: 2386 Status: Offline Project Badges:
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Antibodies are surely going to be the first efficacious therapeutic we have for Covid-19. Here's two good looking examples, one human and one camelid.
----------------------------------------https://www.nature.com/articles/s41467-020-16256-y https://www.cell.com/cell/pdf/S0092-8674(20)3...20304943%3Fshowall%3Dtrue https://www.nytimes.com/2020/05/06/science/ll...ology&pgtype=Homepage A co-author was in the news after being attacked by wingnut lunatics: https://www.washingtonpost.com/climate-enviro...bett-vaccine-coronavirus/ ...KRI please cancel all shadow-banning[Edit 1 times, last edit by Aurum420 at May 8, 2020 3:12:03 PM] |
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Aurum
Master Cruncher The Great Basin Joined: Dec 24, 2017 Post Count: 2386 Status: Offline Project Badges:
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This is a good article on the latest tech used to find neuts:
----------------------------------------https://www.sciencemag.org/news/2020/05/race-antibodies-stop-new-coronavirus ...KRI please cancel all shadow-banning |
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Jim1348
Veteran Cruncher USA Joined: Jul 13, 2009 Post Count: 1066 Status: Offline Project Badges:
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If the antibodies are long-lasting enough, they might even replace vaccines. That is, unless you are lucky enough to find a vaccine that is both long-lasting and covers a variety of strains, then you might have to give a new vaccine shot yearly (as with the flu).
But that is always hit-or-miss. It would appear that the antibodies can be developed, and more importantly tested, more rapidly. |
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Aurum
Master Cruncher The Great Basin Joined: Dec 24, 2017 Post Count: 2386 Status: Offline Project Badges:
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Our bodies have various machines to digest proteins down to amino acids, e.g. digestion and lysosomes. Injected antibodies will only survive a few months. A vaccine trains B cells to make the antibodies. B cells are the antibody factories and each B cell makes exactly one kind of antibody. Some B cells become memory B cells and may last a lifetime.
----------------------------------------As an aside remdesivir stops protein production and not just for the virus. This means that the signals that tell B cells and T cells (kill infected cells) to divide and multiply diminish. Remdesivir will require a careful balancing act between poisoning the patient just enough to slow viral replication but not completely disable the immune response. A very scary prospect. ...KRI please cancel all shadow-banning |
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