Preprint Hypothesis Version 1 This version is not peer-reviewed

Repositioning Chloroquine as Ideal Antiviral Prophylactic against COVID-19 - Time is Now

Version 1 : Received: 16 March 2020 / Approved: 17 March 2020 / Online: 17 March 2020 (15:57:38 CET)

How to cite: Chang, R.; Sun, W. Repositioning Chloroquine as Ideal Antiviral Prophylactic against COVID-19 - Time is Now. Preprints 2020, 2020030279 (doi: 10.20944/preprints202003.0279.v1). Chang, R.; Sun, W. Repositioning Chloroquine as Ideal Antiviral Prophylactic against COVID-19 - Time is Now. Preprints 2020, 2020030279 (doi: 10.20944/preprints202003.0279.v1).

Abstract

The novel coronavirus 2019 (COVID-19) pandemic is rapidly advancing despite public health measures. Pharmaceutical prophylaxis is an established approach to potentially control infectious diseases and is one solution to the urgent public health challenge posed by COVID-19. Screening and development of new vaccines and antivirals is expensive and time consuming while the repositioning of available drugs should receive priority attention as well as international government and agency support. Here we propose an old drug chloroquine (CQ) to be urgently repositioned as an ideal antiviral prophylactic against COVID-19. CQ has ability to block viral attachment and entry to host cells. Its proven clinical efficacy against a variety of viruses including COVID-19 and its current deployment in COVID-19 therapeutic trials strengthens its potential candidacy as a prophylactic. Furthermore, CQ has a long safety record, is inexpensive and widely available. Here we reviewed CQ's antiviral mechanisms, its laboratory efficacy activity against COVID-19, as well as CQ's pharmacokinetics in its established use against malaria and autoimmune diseases to recommend safe and potentially efficacious dose regimens for protection against COVID-19: a pre-exposure prophylaxis of 250-500mg daily and post-exposure prophylaxis at 8mg/kg/day for 3 days. We recommend further urgent research on CQ for COVID-19 prevention and urge that the above regimens be investigated in parallel with mass deployment by relevant agencies in attempts to contain the pandemic without unnecessary regulatory delays as benefits far outweigh risks or costs.

Subject Areas

chloroquine; COVID-19; SARS-CoV2; antiviral; viral prophylaxis

Comments (1)

Comment 1
Received: 21 March 2020
Commenter: DR NEIL RANGEL
The commenter has declared there is no conflict of interests.
Comment: EXCELLENT


Subject: VERY URGENT / SUGGESTION- CHLOROQUINE . HYDROXYCHLOROQUINE PROPHYLAXIS FOR NCOVID-19

KIND ATTENTION
Kindly find an urgent recommendation for - consideration/ concerning CHEMOPROPHYLAXIS against the NCOVID -19 pandemic
I am frustrated by the kind of silly responses and lackadaisical attitude of many- in relation to my suggestion to urgently formulate a policy on chloroquine/hydroxychloroquine prophlyaxis against NCOVID19. People are dying like flies by the 100s and they tell me we need to wait for clinical trials! I believe this intervention will slow transmission, reduce severity and save lives. We used to give chloroquine even empirically in the villages. All I am asking for is a supervised 1 tablet stat or weekly – a harmless dose. 1$ could easily get 100 tabs. This is an emergency and all protocol requirements for a drug trial have to be waived. I am appalled that face masks are not being made mandatory- it makes sense to believe any protection is better than no protection

I THINK MEDICAL PROFESSIONALS THEMSELVES MUST NOW ACTIVELY LOBBY THE HEALTH AUTHORITIES TO RECOMMEND CHLOROQUINE/ HYDROXYCHLOROQUINE PROPHYLAXIS AGAINST NCOVID19- URGENTLY. EVIDENCE FOR USE IS REASONABLY GOOD AND THE DRUG IS SAFE IN SAID DOSES
I HAVE WRITTEN TO EVERY THINKABLE EXCEPT DONALD TRUMP I HAVE NO ACCESS TO - PMs, PRESIDENTS, HEALTH MINISTERS, SECRETARIES, WHO, CDC, MR FAUCCI, MR COLLINS, NIH, LANCET, BMJ, JAMA, NHS, - UK GOV, IRELAND, SINGAPORE, INDIA, HOLLAND, DENMARK, NORDIC, ITALY, FRANCE, PORTUGAL...LETS SEE. I THINK WE ARE RUNNING OUT OF TIME

Will appreciate of my comments can be forwarded widely and to those in authority/ decision – guideline making


DR NEIL DE JESUS RANGEL/ Endocrinologist, Mediclinic Welcare Hospital, Dubai, UAE
[email protected] / +971 557206680

____________

URGENCY STATUS: EXTREMELY URGENT

SUBJECT: URGENTLY CONSIDER WEEKLY CHLOROQUINE/ HYDROXYCHLOROQUINE CHEMOPROPHYLAXIS (PREVENTION) AGAINST THE NOVEL CORONA VIRUS IN GENERAL POPULATION/ AT RISK

FROM: DR NEIL DE JESUS RANGEL/ Endocrinologist, Mediclinic Welcare Hospital, Dubai, UAE
[email protected] / +971 557206680

Greetings

I am a medical doctor based in Dubai, UAE. I have been keenly following treatment protocols evolving over last few days; having worked in a rural area in the past endemic in malaria where chloroquine was used empirically(10 tablets over 3 days) and the drug is considered reasonably safe.

I strongly believe there is a serious and urgent case to make for widespread prophylactic use of chloroquine/ hydroxyl-chloroquine in the general population – a weekly or monthly single tablet. It could be a game-changer with the potential to prevent/delay/ attenuate infections and the spread and importantly finally save lives. Available literature and experience suggests both hydroxyl-chloroquine and chloroquine are effective in inhibiting SARS-CoV-2 infection.

There is no time for a clinical trial and it will need to be used as an experimental/ off-label use for the current pandemic. I am not aware of any literature that suggests prophylactic use in NCOVID-19

I urge health authorities to seriously consider this suggestion and decide on implementing it with hours/ days from now. Off course adequate stocks of these should be retained for those who will benefit most(established symptomatic NCOVID-19 patients/ malaria treatment and other conditions where used for)

Considering the pharmacokinetics and long half life- I believe a single oral dose( to decide based on body weight- suggested 1 tablet for adults- for all individuals should be the starting point AND will not do any harm and will be of net benefit (except those in whom it could be contraindicated- which undoubtedly is a small minority). I BELIEVE THE BENEFITS COULD OUTWEIGH THE RISK OF HARM. KINDLY LIASE URGENTLY WITH EXPERTS AND HEALTH AUTHORITIES ALL OVER THE WORLD AND DECIDE URGENTLY IF THIS MEASURE IS JUSTIFIABLE AND HAD THE POTENTIAL TO PREVENT SPREAD, ATTENUATE INFECTIONS AND SAVE LIVES………………………….Authorities can subsequently decide if follow up doses are needed and the frequency – weekly or monthly/ tracking use with election indelible ink- other means. The medications are cheap and can be mass produced. Those at highest risk of infection/complications; should be the first to receive it. It may benefit long term when repeat infections and reactivations are expected later.

This is not meant to be an invitation to public to self-medicate; rather a recommendation for health authorities to get together quickly and decide on this what I believe could be life saving

I also believe the authorities should encourage the use of face masks by everyone- any protection is better than no protection/ when not available; a home-made one should be used.
Thank you and God bless and keep safe

DR NEIL DE JESUS RANGEL

JUSTIFICATION- CONSIDERATIONS(I quote from 2 sources/ there are many more..)

1) ….oral absorption of CQ and HCQ in humans is very efficient….
2) …..concentrations in the liver, spleen, kidney, and lung reaching levels of 200–700 times higher than those in the plasma….
3) …..with a safe dosage, HCQ concentration in the above tissues is likely to be achieved to inhibit SARS-CoV-2 infection…..
4) ….Contra-indications  QTc > 500 msec  drug interaction; check at http://www.covid19- druginteractions.org (Liverpool) Interaction potential of hydroxychloroquine is likely the same as chloroquine  Myasthenia gravis  Porphyria  Retinal pathology  Epilepsy NB: pregnancy is not a contraindication as such (large safety experience with chloroquine)….
5) ….a single 200 mg oral dose of PLAQUENIL to healthy males, the mean peak blood concentration of hydroxychloroquine was 129.6 ng/mL, reached in 3.26 hours with a half-life of 537 hours (22.4 days)…..
6) Irreversible retinal damage has been observed in some patients who had received hydroxychloroquine sulfate. Significant risk factors for retinal damage include daily doses of hydroxychloroquine sulfate greater than 6.5 mg/kg (5 mg/kg base) of actual body weight, durations of use greater than five years, subnormal glomerular filtration, use of some concomitant drug products such as tamoxifen citrate and concurrent macular disease.
https://www.nature.com/articles/s41421-020-0156-0 / Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro https://epidemio.wiv-isp.be/ID/Documents/Covid19/COVID-19_InterimGuidelines_Treatment_ENG.pdf /INTERIM CLINICAL GUIDANCE FOR PATIENTS SUSPECTED OF/CONFIRMED WITH COVID-19 IN BELGIUM 19 March 2020; Version 4/ 19th Mar 2020
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