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

Trouble in Paradise Surrounding the use of Ivermectin

In nations around the world tension mounts between physicians and caregivers seeking to prescribe what they professionally deem as safe doses of ivermectin, as an off-label treatment for COVID-19 and national health authorities, which for the most part have all taken a hostile and oppositional position against the use of the drug.

Read More »

How Ivermectin became a Target for the ‘Fraud Detectives.’

And why is ivermectin being so negatively targeted by Big Tech and Big Media? One could argue conflict of interest plays a major role, given how intertwined they are with Big Pharma and the far-reaching grasp of the BMGF. A cheap and effective early treatment for Covid-19, like ivermectin, can be seen as a significant threat to the financial interests of those involved with Covid vaccines and expensive anti-viral drugs.

Read More »

Canada: Alberta Failing on COVID-19 Vaccines and Treatment

Numerous studies and clinical observation of thousands of patients has indicated that Ivermectin is highly effective in this regard. Even low dose studies that were designed to reach the conclusion that ivermectin was not effective found a signal that indicated that Ivermectin effectively interacted with the COVID virus molecule to prevent or lessen replication of the virus.”

Read More »