Saturday, October 1, 2022

Why Hydroxychloroquine works for Covid: The same reason Ivermectin works!

Hydroxychloroquine interferes with Nucleocapsid Protein N.... and Ivermectin does the same thing. And so does Artemisinin. You can read more about that here: https://realcovidresearch.blogspot.com/2022/09/what-do-ivermectin-and-artemisinin-aka.html

Check out this paper:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9214679/

2022 Jun; 14(3): 709–715.

Published online 2022 Jun 22. doi: 10.1007/s12551-022-00957-3

PMCID: PMC9214679

PMID: 35756710

A review of the effects of ATP and hydroxychloroquine on the phase separation of the SARS-CoV-2 nucleocapsid protein

Mei Dang and Jianxing Song corresponding author

Author information Article notes Copyright and License information Disclaimer

Here's an excerpt worth noting:

CQ disrupts the interaction of SARS-CoV-2 N protein with nucleic acids and LLPS

Hydroxychloroquine (HCQ) (Fig. 1e) has been proposed for clinically combating the SARS-CoV-2 pandemic (Roldan et al. 2020; Satarker et al. 2020). Very recently, a clinical study in Singapore demonstrated that oral HCQ could indeed prevent the SARS-CoV-2 infection in the high transmission environments (Seet et al. 2921). On the other hand, the mechanisms for its anti-SARS-CoV-2 activity remain poorly understood and previously no viral protein has been experimentally identified to interact with HCQ. Indeed, all the actions of HCQ have been proposed to target the sites on the host cells including the interference in the endocytic pathway, blockade of sialic acid receptors, restriction of pH-mediated S protein cleavage at the ACE2-binding site, and prevention of cytokine storm.

Very unexpectedly, our NMR study recently decrypted that HCQ could in fact specifically bind both NTD (I of Fig. 2a) and CTD (I of Fig. 2b) with dissociation constants (Kds) of 112.1 and 57.1 μM respectively, which consequently inhibited the interactions of N protein with nucleic acids as well as dissolved its LLPS induced by nucleic acids (Dang and Song 2021; Song 2021). Moreover, with NMR-derived constraints, the structures of the HCQ-NTD and HCQ-CTD complexes have been successfully constructed. In the complexes, while ATP and HCQ bind the pockets of NTD with an overlap over their aromatic rings (II and III of Fig. 2a), the distinctive pockets were identified on the dimeric CTD to respectively bind ATP and HCQ (II and III of Fig. 2b). Noticeably in the HCQ-CTD complex, two HCQ molecules are bound with two distinctive pockets but within a cleft on the same side of the dimeric CTD structure, and this binding appears to be mainly driven by the insertion of the aromatic ring of HCQ into the CTD pockets.

https://pubmed.ncbi.nlm.nih.gov/32469265/

Docking study of chloroquine and hydroxychloroquine interaction with RNA binding domain of nucleocapsid phospho-protein - an in silico insight into the comparative efficacy of repurposing antiviral drugs

Muhammad Amin 1, Ghazanfar Abbas 1

Affiliations

PMID: 32469265
DOI: 10.1080/07391102.2020.1775703

Abstract

Recent outbreak of novel Coronavirus disease () pandemic around the world is associated with severe acute respiratory syndrome. The death toll associated with the pandemic is increasing day by day. SARS-CoV-2 is an enveloped virus and its N terminal domain (NTD) of Nucleocapsid protein (N protein) binds to the viral (+) sense RNA and results in virus ribonucleoprotien complex, essential for the virus replication. The N protein is composed of a serine-rich linker region sandwiched between NTD and C terminal (CTD). These terminals play a role in viral entry and its processing post entry. The NTD of SARS-CoV-2 N protein forms orthorhombic crystals and binds to the viral genome. Therefore, there is always a quest to target RNA binding domain of nucleocapsid phosphoprotein (NTD-N-protein which in turn may help in controlling diseases caused by SARS-CoV-2 in humans. The role of Chloroquine and Hydroxychloroquine as potential treatments for is still under debate globally because of some side effects associated with it. This study involves the In silico interactions of Chloroquine and Hydroxychloroquine with the NTD-N-protein of SARS-CoV-2. With the help of various computational methods, we have explored the potential role of both of these antiviral drugs for the treatment of patients by comparing the efficacy of both of the drugs to bind to NTD-N-protein. In our research Hydroxychloroquine exhibited potential inhibitory effects of NTD-N-protein with binding energy -7.28 kcal/mol than Chloroquine (-6.30 kcal/mol) at SARS-CoV-2 receptor recognition of susceptible cells. The outcomes of this research strongly appeal for in vivo trials of Hydroxychloroquine for the patients infected with . Furthermore, the recommended doses of Hydroxychloroquine may reduce the chances of catching to the healthcare workers and staff who are in contact with or delivering direct care to coronavirus patients as long as they have not been diagnosed with . We further hypothesize that the comparative NTD-N-protein -drug docking interactions may help to understand the comparative efficacy of other candidate repurposing drugs until discovery of a proper vaccine.Communicated by Ramaswamy H. Sarma.

Keywords: Coronaviruses; RNA binding domain of nucleocapsid phosphoprotein; SARS-CoV-2; chloroquine; docking studies; hydroxychloroquine.

Cited by

Potential Coronaviral Inhibitors of the Nucleocapsid Protein Identified In Silico and In Vitro from a Large Natural Product Library.
Pohler A, Abdelfatah S, Riedl M, Meesters C, Hildebrandt A, Efferth T.Pharmaceuticals (Basel). 2022 Aug 24;15(9):1046. doi: 10.3390/ph15091046.PMID: 36145267 Free PMC article.

WHAT WORKS FOR COVID... and what DOESN'T