The second reason is even more salient: the great majority of people who have recovered during the COVID-19 pandemic did so because they raised their own neutralizing antibodies to the virus There is, for example, a canine coronavirus vaccine available, although one has to note immediately that it�s for an enteric virus, not a respiratory one, and that it itself is of no use whatsoever (in dogs or in people) against the COVID-19 epidemic

One of the small-molecule drugs that’s getting attention as a possible coronavirus treatment is Ivermectin, which is an interesting story from a couple of different directions I’ve been getting some inquiries about it, so I thought it was time to have a look Ivermectin and COVID-19: So what is this compound doing in the news with the coronavirus? Its ion-channel mechanism of action against parasites has no application to viruses But it has been shown several times to have activity in cell assays against Dengue infection and to reduce viral loads in the mosquito vectors (see this paper and references therein), although the reasons for this are still unknown There have been some human studies for efficacy, but all I can find out is that a preliminary read showed no reduction of viral load in the infected patients, and there seems to have been no update But since denguevirus is also a single-strand positive-sense RNA virus, Ivermectin has come up as a possible coronavirus drug, mechanism or not

This, though, is an official organ of the Chinese state – none more so – showing all sorts of white-fog-spraying devices being deployed outdoors, with the caption “Full-front disinfection work has started in #Wuhan, an effort to contain the spread of #coronavirus“ Maybe there’s something in the mix that someone thinks will do some good against coronavirus particles – I doubt if they’re correct, if so – or maybe the whole thing is just meant to show that the Authorities Are Doing Something

There’s a lot of work being done on antibodies for the coronavirus and on the protein domains they recognize This of course has bearing both on the idea of monoclonal antibody therapies and for the vaccines that are in development, so let’s have a look at the new data For reference, here’s a background post on some of the proteins that the virus makes and the mutations that have been spotted in them, here’s my post on the basics of antibodies and immunology as relating to the epidemic, with an update here, and here’s my earlier post on monoclonal antibodies as a treatment, now updated with some new items

Antibodies as a therapy Let’s have a look at what is (in my opinion) probably our best shot at a reasonably short-term targeted therapy against the COVID-19 epidemic: the possibility of using monoclonal antibodies

I surveyed the coronavirus vaccine landscape in this post, and then detailed some of the larger efforts in the field here (several updates have been added to that one since its initial posting) Now it�s time to look at several programs that aren�t in either of those, but still have plenty of serious science behind them For an example of a relatively new technology that�s now in use for human patients, there�s the VSV (vesicular stomatitis virus) platform, which was used to produce the Ebola vaccine now manufactured by Merck Stat has an excellent long-form article from earlier this year about how this came about, and it�s well worth a read, both for the history itself and as a look into the ups and downs of vaccine research in general The Yale team behind that one had developed a promising vaccine candidate for the SARS coronavirus during its epidemic, and they�re using those lessons in their current work If you look at that second link above on vaccine candidates, you will note that there are several using adenovirus vectors � this is conceptually the same sort of thing, but using a livestock virus (VSV) instead of human or primate-associated adenoviruses I don�t know if the Yale team has partnered with anyone yet, but I should also mention another connection of theirs, a spinoff company called CaroGen that has another engineered virus platform that is also being put to use against SARS-CoV-2 These projects are aiming at FDA approval for Phase I trials, but there�s no word yet on what such an application might go in

Derek Lowe draws lessons for today from a history of scientists’ experimental hacks. Derek Lowe draws lessons for today from a history of scientists’ experimental hacks.

The lipid kinase phosphoinositide 3-kinase γ (PI3Kγ) has attracted attention as a potential target to treat a variety of autoimmune disorders, including multiple sclerosis, due to its role in immune modulation and microglial activation. By minimizing the number of hydrogen bond donors while targeting a previously uncovered selectivity pocket adjacent to the ATP binding site of PI3Kγ, we discovered a series of azaisoindolinones as selective, brain penetrant inhibitors of PI3Kγ. This ultimately led to the discovery of 16, an orally bioavailable compound that showed efficacy in murine experimental autoimmune encephalomyelitis (EAE), a preclinical model of multiple sclerosis.

Antibodies, RNA and gene therapy don't necessarily compete with small molecule drugs - and they all rely on chemistry as well.

We're going to need a bigger compound deck...

ADVERTISEMENT RETURN TO ISSUEEditorialNEXTIntroducing Biochemistry to BedsideDerek B. Lowe*View Author Information Chemical Biology and Therapeutics, Novartis Institutes for BioMedical Research Inc., 250 Massachusetts Avenue, Cambridge, Massachusetts 02139-4133, United States*E-mail: [email protected]Cite this: Biochemistry 2018, 57, 5, 469Publication Date (Web):February 6, 2018Publication History Received5 December 2017Published online6 February 2018Published inissue 6 February 2018https://doi.org/10.1021/acs.biochem.7b01217Copyright © 2018 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views1807Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (187 KB) Get e-AlertsSUBJECTS:Biochemistry,Drug discovery,Inhibitors,Modulators,Peptides and proteins Get e-Alerts

Derek Lowe enjoys Mark Miodownik’s sparkling investigation of liquids. Derek Lowe enjoys Mark Miodownik’s sparkling investigation of liquids.

Software that devises effective schemes for synthetic chemistry has depended on the input of rules from researchers. A system is now reported in which an artificial-intelligence program learns the rules for itself. Software that devises effective schemes for synthetic chemistry has depended on the input of rules from researchers. A system is now reported in which an artificial-intelligence program learns the rules for itself.

This paper presents the overall design for large (\(\sim \)400 mm aperture) reference blackbody cavities currently under development at the Science and Technology Facilities Council Rutherford Appleton Laboratory Space Department (STFC RAL Space), in collaboration with the National Physical Laboratory (NPL). These blackbodies are designed to operate in vacuum over a temperature range from 160 K to 370 K, with an additional capability to operate at \(\sim \)100 K as a point of near-zero radiance. This is a challenging problem for a single blackbody. The novel thermal design presented in this paper enables one target that can physically achieve and operate successfully at both thermal extremes, whilst also meeting stringent temperature gradient requirements. The overall blackbody design is based upon a helium gas-gap heat switch and modified to allow for variable thermal conductance. The blackbody design consists of three main concentric cylinder components—an inner cavity (aluminium alloy), a radiation shield (aluminium) and an outer liquid nitrogen (\(\hbox {LN}_{2}\)) jacket (stainless steel). The internal surface of the cavity is the effective radiating surface. There is a helium gas interspace surrounding the radiation shield and enclosed by the \(\hbox {LN}_{2}\) jacket and the inner cavity. The blackbodies are now at a mature stage of development. In this paper, the overall design, focusing upon the thermal design solution, is detailed. This paper will also concern the full-scale prototype breadboard model, for which results on thermal stability, spatial gradients and other sensitivities will be presented.

There are currently no treatments for life-threatening infections caused by human polyomaviruses JCV and BKV. We therefore report herein the first crystal structure of the hexameric helicase of JCV large T antigen (apo) and its use to drive the structure-based design of dual JCV and BKV ATP-competitive inhibitors. The crystal structures obtained by soaking our early inhibitors into the JCV helicase allowed us to rapidly improve the biochemical activity of our inhibitors from 18 μM for the early 6-(2-methoxyphenyl)- and the 6-(2-ethoxyphenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole hits 1a and 1b to 0.6 μM for triazolopyridine 12i. In addition, we were able to demonstrate measurable antiviral activity in Vero cells for our thiazolopyridine series in the absence of marked cytotoxicity, thus confirming the usefulness of this approach.

The chemical nature of biomolecular interactions can no longer be ignored.

Does simple gene-editing mean the end of traditional medicinal chemistry? Probably not.

Computer-assisted drug design always looks like it's just about to work, says Derek Lowe, but the reality is complicated.

An occasional foray into uncharted territory is the hot sauce of medicinal chemistry, says Derek Lowe.