Source: Research Square, Full Text PDF

DOI: 10.21203/rs.3.rs-621646/v1

Abstract

Great efforts have led to successfully developing the spike-based vaccines but challenges still exist to completely terminate the SARS-CoV-2 pandemic. SARS-CoV-2 nucleocapsid (N) protein plays the essential roles in almost all key steps of the viral life cycle, thus representing a top drug target. Almost all key functions of N protein including liquid-liquid phase separation (LLPS) depend on its capacity in interacting with nucleic acids.

Therefore, only the variants with their N proteins functional in binding nucleic acids might survive and spread in evolution and indeed, the residues critical for binding nucleic acids are highly conserved. Very recently, hydroxychloroquine (HCQ) was shown to prevent the transmission in a large-scale clinical study in Singapore but so far, no specific SARS-CoV-2 protein was experimentally identified to be targeted by HCQ.

Here by NMR, we unambiguously decode that HCQ specifically binds NTD and CTD of SARS- CoV-2 N protein with Kd of 112.1 and 57.1 μM respectively to inhibit their interaction with nucleic acid, as well as to disrupt LLPS essential for the viral life cycle. Most importantly, HCQ-binding residues are identical in SARS-CoV-2 variants and therefore HCQ is likely effective to them all.

The results not only provide a structural basis for the anti-SARS-CoV-2 activity of HCQ, but also renders HCQ to be the first known drug capable of targeting LLPS.

Furthermore, the unique structure of the HCQ-CTD complex decodes a promising strategy for further design of better anti-SARS-CoV-2 drugs from HCQ. Therefore, HCQ is a promising candidate to help terminate the pandemic.

KEYWORDS
Hydroxychloroquine (HCQ), SARS-CoV-2, Nucleocapsid (N) protein, Liquidliquid phase separation (LLPS), NMR spectroscopy

Get the full text document in PDF here




This doctor cured 5000 corona patients with hydroxychloroquine

Hydroxychloroquine is the smartest drug in history

How hydroxychloroquine works at the cellular level

New study reveals success of hydroxychloroquine as COVID treatment

Doctor’s Advice on Early Treatment for COVID-19

Journal Editors Resign Over Suppression of Ivermectin Research Paper – The Chloroquine Wars Part XXVII

Is the vaccine safe? Undoing the spin on the vaccine. We have safe and effective treatment options for COVID.

Share on facebook
Share on twitter
Share on whatsapp
On Trend

Latest Stories

A Conversation With Dr. Brian Tyson – The Chloroquine Wars Part XLI

The data from the vaccine trials must be recalculated under the lens that some of the serious adverse events (SAEs) should be treated as COVID-19 cases.
There may not be any vaccine efficacy in the data at all if some of the post-vaccination deaths are due to vaccine-induced COVID-19. It could even be the case that the mortality efficacy goes negative. My implied lives saved calculations put this easily in the realm of possibility. The only way to know is for authorities to organize and compile the data. And while a risk analysis is certainly due after more than six months of hundreds of millions of doses delivered, there is little indication authorities have bothered with the process. That’s more than a bit unsettling.

Read More »

Dr. Brian Tyson, USA: Hydroxychloroquine – Data, Strategies and Success Treating over 6000 Covid Patients

We continue to delve extensively into the COVID-19 data with esteemed statistician, Mathew Crawford. In this episode, we take a closer look at the use of early treatment and its success. Mathew has been researching the data from Dr. Brian Tyson, who has successfully treated over 6000 patients who contracted COVID throughout the pandemic. It is my great honor to have Dr. Tyson here on this episode to not only discuss the data, but also the strategies that he has been using throughout the pandemic.

Read More »