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Fighting Coronavirus – an update on Remdesivir by Gilead

Posted by admin

Great to see the recent early clinical trial results for Remdesivir showing some benefit in a small study of hospitalised infected patients.(1)

The results of larger more detailed trials will be eagerly awaited. If effective the need to supply significant amounts of this drug will be essential.

The synthesis of Remdesivir is a long linear process, although the cost per dose is relatively cheap. Gilead have made significant improvements to the manufacturing route, reducing it from one year to six months.(2)

If Remdesivir is shown to be effective in larger trials, the demand for the drug will significantly outstrip the ability to supply.

Gilead stated they currently have ~1.5 million doses available, which could provide ~140,000 treatment courses. As the global population is ~7 billion, then supply needs to be significantly increased.(3)

The drug was originally designed to be given as an intravenous infusion, meaning anyone receiving treatment would need this to happen in a suitably conducted environment.

In order to allow greater dosing to the general population, assessment of the ability to dose the drug orally, or via a more straightforward manner need to be looked into, as a matter of urgency. Reformulation or other dosing regimens might provide suitable alternatives.

As mentioned in our last post, it would be great to see the chemistry community working collaboratively to come up with alternative approaches that could impact supply of this and other potentially pivotal drugs in the fight to keep this virus contained.

References:

(1) Data on 53 Patients Treated With Investigational Antiviral Remdesivir Through the Compassionate Use Program Published in New England Journal of Medicine – https://www.gilead.com/news-and-press/press-room/press-releases/2020/4/data-on-53-patients-treated-with-investigational-antiviral-remdesivir-through-the-compassionate-use-program-published-in-new-england-journal-of-medici 

(2) Working to Supply Remdesivir for COVID-19 – https://www.gilead.com/purpose/advancing-global-health/covid-19/working-to-supply-remdesivir-for-covid-19

(3) 1.5 Million Doses of Experimental Coronavirus Drug Remdesivir Donated by Biotech Firm Gilead – https://www.newsweek.com/15-million-doses-experimental-coronavirus-drug-remdesivir-donated-biotech-firm-gilead-1496247

Press Release – Curza and o2h discovery announce a multi-FTE chemistry collaboration against gram negative

Impacting COVID-19 – Opportunities for Chemists

Posted by admin

Dear Chemists,

We’re all aware of the situation we all are currently facing. We do these jobs for a love of chemistry and to steal a punchline from my old employer, making a meaningful difference to patients humanity.

Now is the time when we can openly collaborate to do our part and potentially protect many lives.

Gilead’s Remdesivir looks to be the most promising compound to help tackle COVID-19 in the short/medium term, along with a number of molecules that are in clinical development or repurposing of marketed drugs (including hydroxychloroquine, camostat etc., to name a few).

If any of these show positive effects, then supply will not be able to meet demand.

Remdesivir is patented and these will be active for many years. However, companies like Abbvie have already agreed to open up competition to its HIV med Kaletra (Aluvia).

I’m sure Gilead’s chemists have come up with robust routes for Remdesivir, but novel manufacturing routes will need to developed very rapidly, so the available chemical pool can be used as efficiently and innovatively as possible.

As a community that is used to innovating and solving problems, we can work openly and collaboratively, to provide rapid solutions.

From my reading of the literature the lactone below is a key intermediate in the synthesis of Remdesivir.

lactone - o2h discovery

Further literature review shows the lactone can in turn be made from:

Lactone - o2h discovery

This bicycle is an interesting structure, but more importantly, it can be synthesised from lignocellulose, which is the most abundant and renewable biomass on earth. A number of chemistry groups have evaluated this process in the past, but conversion and yields still remain modest.

We have some of the greatest minds on the planet working across chemistry. Solving problems like these through open source discussions and experiments will undoubtedly put us in a stronger position over the coming months to increase the number of available treatment options and hopefully save many lives.

The o2h group supports early stage therapeutic companies through collaborative drug discovery research, investment and incubation, with teams in Cambridge, UK and Ahmedabad in India. We are prepared to help this cause in any way we can.

If plans can be rapidly collated, I’m sure governments across the world would see this effort as essential and allow chemical shipments and key research to be continued.

Let’s make sure when we look back in six months’ time we can be proud of our collective legacy and what we were able to deliver for ourselves, families, colleagues, friends and humanity.

Andy Morley

Chief Scientific Officer, o2h group

(Img source: https://news.ucr.edu/)

Press Release – Curza and o2h discovery announce a multi-FTE chemistry collaboration against gram negative