This is a reach, perhaps. I'm trying to understand how ivermectin can help fight the virus.
Researchers at The University of Texas Health Science Center (San Antonio, TX, USA) resolved the structure of an enzyme called nsp16, which the coronavirus produces and then uses to modify its messenger RNA cap. These modifications fool the cell, as a result of which the viral messenger RNA becomes considered as part of the cell’s own code and not foreign. Deciphering the 3D structure of nsp16 paves the way for rational design of antiviral drugs for COVID-19 and other emerging coronavirus infections, according to Dr. Yogesh Gupta, PhD, the study lead author from the Joe R. and Teresa Lozano Long School of Medicine at UT Health San Antonio. The drugs, new small molecules, would inhibit nsp16 from making the modifications. The immune system would then pounce on the invading virus, recognizing it as foreign.
A possible ivermectin tie-in is suggested by the study A Combination of Ivermectin and Doxycycline Possibly Blocks the Viral Entry and Modulate the Innate Immune Response in COVID-19 Patients, posted to this sub here.
Ivermectin also possess significant binding affinity with NSP3, NSP10, NSP15 and NSP16 which helps virus in escaping from host immune system. Molecular dynamics simulation study shows that binding of the Ivermectin with Mpro, Spike, NSP3, NSP16 and ACE2 was quiet stable.
In a table in that study, the predicted binding energy of ivermectin against NPS16 is -8.3 (a high number, meaning it's likely to happen, I believe) and the predicted inhibition constant is .81.
All the 5 potential protease inhibitors viz. remdesivir, nelfinavir, lopinavir, ritonavir, and ketoamide got docked onto the predicted 3D model of protease of COVID-19 with a negative dock energy value as shown in Fig. 1. The best recorded binding energy value was obtained for nelfinavir (− 7.54 kcal mol−1).
Figure 1 has the binding energy for those 5 drugs, and nelfinavir has the highest number -- so I infer that higher binding energy is better. Note that ivermectin's -8.3 is higher still.
What is the import of ivermectin's predicted inhibition constant of .81?
Looking it up:
The inhibitor constant, Ki, is an indication of how potent an inhibitor is; it is the concentration required to produce half maximum inhibition. Plotting 1/v against concentration of inhibitor at each concentration of substrate (the Dixon plot) gives a family of intersecting lines.
That doesn't help me. :(
Deciding I need help with the science -- I made a long post to /r/covid19 about this. I hope some people respond!
[-] TrumpLyftAlles | 1 points | Aug 08 2020 22:31:51
This is a reach, perhaps. I'm trying to understand how ivermectin can help fight the virus.
Researchers at The University of Texas Health Science Center (San Antonio, TX, USA) resolved the structure of an enzyme called nsp16, which the coronavirus produces and then uses to modify its messenger RNA cap. These modifications fool the cell, as a result of which the viral messenger RNA becomes considered as part of the cell’s own code and not foreign. Deciphering the 3D structure of nsp16 paves the way for rational design of antiviral drugs for COVID-19 and other emerging coronavirus infections, according to Dr. Yogesh Gupta, PhD, the study lead author from the Joe R. and Teresa Lozano Long School of Medicine at UT Health San Antonio. The drugs, new small molecules, would inhibit nsp16 from making the modifications. The immune system would then pounce on the invading virus, recognizing it as foreign.
A possible ivermectin tie-in is suggested by the study A Combination of Ivermectin and Doxycycline Possibly Blocks the Viral Entry and Modulate the Innate Immune Response in COVID-19 Patients, posted to this sub here.
Ivermectin also possess significant binding affinity with NSP3, NSP10, NSP15 and NSP16 which helps virus in escaping from host immune system. Molecular dynamics simulation study shows that binding of the Ivermectin with Mpro, Spike, NSP3, NSP16 and ACE2 was quiet stable.
In a table in that study, the predicted binding energy of ivermectin against NPS16 is -8.3 (a high number, meaning it's likely to happen, I believe) and the predicted inhibition constant is .81.
In Binding site analysis of potential protease inhibitors of COVID-19 using AutoDock:
All the 5 potential protease inhibitors viz. remdesivir, nelfinavir, lopinavir, ritonavir, and ketoamide got docked onto the predicted 3D model of protease of COVID-19 with a negative dock energy value as shown in Fig. 1. The best recorded binding energy value was obtained for nelfinavir (− 7.54 kcal mol−1).
Figure 1 has the binding energy for those 5 drugs, and nelfinavir has the highest number -- so I infer that higher binding energy is better. Note that ivermectin's -8.3 is higher still.
What is the import of ivermectin's predicted inhibition constant of .81?
Looking it up:
The inhibitor constant, Ki, is an indication of how potent an inhibitor is; it is the concentration required to produce half maximum inhibition. Plotting 1/v against concentration of inhibitor at each concentration of substrate (the Dixon plot) gives a family of intersecting lines.
That doesn't help me. :(
Deciding I need help with the science -- I made a long post to /r/covid19 about this. I hope some people respond!
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