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Since this is going to be a post about the coronavirus, let's start off with this PSA: wash your hands. These viruses have a lipid envelope that is crucial to their structure and function, and soaps and detergents are thus very effective at inactivating them. It's fast, it's simple, and it's one of the more useful things that any individual can do under these conditions.

The decision to delay closing schools and introduce other strict measures to combat coronavirus has been defended by England's deputy chief medical officer.

Dr Jenny Harries said experts are assessing new cases on an hourly basis to achieve a "balanced response".

The NHS has unveiled a range of measures as part of its response to try to stop fake news being spread about coronavirus on the internet.

Searches for "coronavirus" on Google, Facebook and YouTube will now promote information from the National Health Service or the World Health Organization.

The NHS said it had worked with Twitter to take down an account claiming to be a hospital and spreading false information, while it is also speaking out against homeopaths promoting false treatments online.

Health Secretary Matt Hancock said the actions meant the public could access accurate health information "which is more crucial than ever as we continue our response to coronavirus".

The UK is currently in the first phase - "containment" - of the government's four-part plan.

On Monday, health officials said people who showed "even minor" signs of respiratory tract infections or a fever would soon be told to self-isolate for seven days in an effort to tackle the outbreak.

The change in advice could happen within the next 10 to 14 days, the UK's chief medical adviser Prof Chris Whitty said.

It came after researchers in the US found it took five days for most people with coronavirus to show symptoms.

Prime Minister Boris Johnson also suggested the elderly and vulnerable could be asked to stay home in the near future.

Days after the coronavirus outbreak prompted Apple CEO Tim Cook to let his employees work from home, 9to5Mac reported that the company's retail and hourly workers are getting unlimited sick leave if they experience the pneumonia-like symptoms linked to the disease.

These workers won't need to give managers a doctor's note either. Apple Stores are remaining open despite the outbreak, but 9to5Mac noted that company is canceling some Today at Apple sessions and other gatherings to limit crowds.

Italian Prime Minister Giuseppe Conte announced Monday that the government has extended internal travel restrictions to the entire country until April 3, after initially locking down the country's northern region in an effort to contain the coronavirus.

Why it matters: It's an extreme measure that effectively locks down 60 million people in one of the most populated countries in Europe, where more people have tested positive for the coronavirus than any country outside of China. Conte also announced that all public gatherings and sporting events would be banned.

Chinese President Xi Jinping has visited Wuhan, the epicentre of the coronavirus outbreak, the first time he has done so since the epidemic began and a sign that Beijing believes its efforts to control the virus are working.

His arrival in the city comes after its spread in mainland China has sharply slowed in the past week and as attention has turned to preventing imported infections from overseas hot spots such as Iran, Italy and South Korea.

Authorities in China's Hubei said on Tuesday they will implement a "health code" mobile-phone-based monitoring system to start allowing people to travel within the province, as it tries to get life back to normal.

The statement, published on the government's website, said the move was aimed at promoting the resumption of work and production.

China's President Xi Jinping arrived in the provincial capital, Wuhan, on Tuesday for his first visit and is meeting medical workers and others involved in the fight against the virus.

The Food and Drug Administration said Monday it has sent warning letters to televangelist Jim Bakker and six companies for selling unapproved coronavirus drugs and treatment products.

"The FDA considers the sale and promotion of fraudulent COVID-19 products to be a threat to the public health. We have an aggressive surveillance program that routinely monitors online sources for health fraud products, especially during a significant public health issue such as this one," FDA Commissioner Stephen M. Hahn said in announcing the enforcement actions.

The products include teas, essential oils, tinctures and colloidal silver, which have been cited as not safe or effective for treating any disease, the agency said in a statement with the Federal Trade Commission.

The FDA said it was particularly worried that the products may cause people to delay or stop appropriate treatment, "leading to serious and life-threatening harm."

Let's take inventory on the therapies that are being developed for the coronavirus epidemic. Here is a very thorough list of at Biocentury, and I should note that (like Stat and several other organizations) they're making all their Covid-19 content free to all readers during this crisis. I'd like to zoom in today on the potential small-molecule therapies, since some of these have the most immediate prospects for use in the real world.

The ones at the front of the line are repurposed drugs that are already approved for human use, for a lot of obvious reasons. The Biocentury list doesn't cover these, but here's an article at Nature Biotechnology that goes into detail. Clinical trials are a huge time sink – they sort of have to be, in most cases, if they're going to be any good – and if you've already done all that stuff it's a huge leg up, even if the drug itself is not exactly a perfect fit for the disease. So what do we have? The compound that is most advanced is probably remdesivir from Gilead, at right. This has been in development for a few years as an RNA virus therapy – it was originally developed for Ebola, and has been tried out against a whole list of single-strand RNA viruses. That includes the related coronaviruses SARS and MERS, so Covid-19 was an obvious fit.

The compound is a prodrug – that phosphoramide gets cleaved off completely, leaving the active 5-OH compound GS-44-1524. It mechanism of action is to get incorporated into viral RNA, since it's taken up by RNA polymerase and it largely seems to evade proofreading. This causes RNA termination trouble later on, since that alpha-nitrile C-nucleoside is not exactly what the virus is expecting in its genome at that point, and thus viral replication is inhibited.

There are five clinical trials underway (here's an overview at Biocentury). The NIH has an adaptive-design Phase II trial that has already started in Nebraska, with doses to be changed according to Bayesian readouts along the way. There are two Phase III trials underway at China-Japan Friendship Hospital in Hubei, double-blinded and placebo-controlled (since placebo is, as far as drug therapy goes, the current standard of care). And Gilead themselves are starting two open-label trials, one with no control arm and one with an (unblinded) standard-of-care comparison arm. Those might read out first, depending on when they get off the ground, but will be only rough readouts due to the fast-and-loose trial design. The two Hubei trials and the NIH one will add some rigor to the process, but I'm not sure when they're going to report. My personal opinion is that I like the chances of this drug more than anything else on this list, but it's still unlikely to be a game-changer.

There's an RNA polymerase inhibitor (favipiravir) from Toyama, at right, that's in a trial in China. It's a thought – a broad-spectrum agent of this sort would be the sort of thing to try. But unfortunately, from what I can see, it has already turned up as ineffective in in vitro tests. The human trial that's underway is honestly the sort of thing that would only happen under circumstances like the present: a developing epidemic with a new pathogen and no real standard of care. I hold out little hope for this one, but given that there's nothing else at present, it probably should be tried. As you'll see, this is far from the only situation like this.

[...] There are several other known antiviral drugs [that] are being tried in China, but I don't have too much hope for those, either. The neuraminidase inhibitors such as oseltamivir (better known as Tamiflu) were tried against SARS and were ineffective; there is no reason to expect anything versus Covid-19 although these drugs are a component of some drug cocktail trials. The HIV protease therapies such as darunavir and the combination therapy Kaletra are in trials, but that's also a rather desperate long shot, since there's no particular reason to think that they will have any such protease inhibition against what this new virus has to offer (and indeed, such agents weren't much help against SARS in the end, either). The classic interferon/ribavirin combination seems to have had some activity against SARS and MERS, and is in two trials from what I can see. That's not an awful idea by any means, but it's not a great one, either: if your viral disease has interferon/ribavirin as a front line therapy, it generally means that there's nothing really good available. No, unless we get really lucky none of these ideas are going to slow the disease down much.

There are a few other repurposed-protease-inhibitors ideas out there, such as this one. (Edit: I had seen this paper but couldn't track it down, so thanks to those who sent it along). This paper suggests that the TMPRSS2 protease is important for viral entry on the human-cell-side of the process, a pathway that has been noted for other coronaviruses. And it points out that there is a an approved inhibitor (in Japan) for this enzyme (camostat), so that would definitely seem to be worth a trial, probably in combination with remdesivir.

That's about it for the existing small molecules, from what I can see. What about new ones? Don't hold your breath, is all I can say. A drug discovery program from scratch against a new pathogen is, as many readers here well know, not a trivial exercise. As this Bloomberg article details, many such efforts in the past (small molecules and vaccines alike) have come to grief because by the time they had anything to deliver the epidemic itself had passed. Indeed, Gilead's remdesivir had already been dropped as a potential Ebola therapy.

You will either need to have a target in mind up front or go phenotypic. For the former, what you'd see are better characterizations of the viral protease and more extensive screens against it. Two other big target areas are viral entry (which involves the "spike" proteins on the virus surface and the ACE2 protein on human cells) and viral replication. To the former, it's worth quickly noting that ACE2 is so much unlike the more familiar ACE protein that none of the cardiovascular ACE inhibitors do anything to it at all. And targeting the latter mechanisms is how remdesivir was developed as a possible Ebola agent, but as you can see, that took time, too. Phenotypic screens are perfectly reasonable against viral pathogens as well, but you'll need to put time and effort into that assay up front, just as with any phenotypic effort, because as anyone who does that sort of work will tell you, a bad phenotypic screen is a complete waste of everyone's time.

[...] All this means that any new-target new-chemical-matter effort against Covid-19 (or any new pathogen) is going to take years, and there is just no way around that. This puts small molecules in a very bimodal distribution: you have the existing drugs that might be repurposed, and are presumably available right now. Nothing else is! At the other end, for completely new therapies you have the usual prospects of drug discovery: years from now, lots of money, low success rate, good luck to all of us. The gap between these two could in theory be filled by vaccines and antibody therapies (if everything goes really, really well) but those are very much their own area and will be dealt with in a separate post.

Turkey has allowed millions of undocumented migrants to cross into Greece as the coronavirus takes hold in Iran and enters Europe. With more countries around the world reporting cases of infection Turkey, going back on its billion dollar agreement to contain undocumented migrants at its borders, is now assisting migrants to enter Greece. Greek officials are already struggling to manage the undocumented arrivals and provide sufficient care to them in the wake of what looks like a global pandemic. With hundreds of thousands of migrants trying to enter the country locals are repelling boats and border guards are shooting riot gas. At least one undoc has been killed trying to cross the Greek border. The situation is causing panic in Greece as people prepare for the impact of Covid-19.

The EPA-registered disinfectant products on this list have qualified under EPA's emerging viral pathogen program for use against SARS-CoV-2, a coronavirus that causes COVID-19. Coronaviruses are enveloped viruses, meaning they are one of the easiest types of viruses to kill with the appropriate disinfectant product. The emerging viral pathogen guidance was triggered for SARS-CoV-2 on January 29, 2020.

EPA strongly recommends following the product label use directions for enveloped viruses, as indicated by the approved emerging viral pathogen claim on the master label. If the directions for use for viruses/virucidal activity list different contact times or dilutions, use the longest contact time or most concentrated solution.

• List N: Disinfectants for Use Against SARS-CoV-2 (PDF)(7 pp, 270 K, March 3, 2020)

More than 100,000 people have been infected with a new coronavirus that has spread widely from its origin in China over the past few months. More than 3,000 have already died. Our comprehensive guide for understanding and navigating this global public health threat is below.

[...] You should be concerned and take this seriously. But you should not panic.

This new coronavirus—dubbed SARS-CoV-2—is unquestionably dangerous. It causes a disease called COVID-19, which can be deadly, particularly for older people and those with underlying health conditions. While the death rate among infected people is unclear, even some current low estimates are seven-fold higher than the estimate for seasonal influenza.

[...] Coronaviruses are a large family of viruses that get their name from the halo of spiked proteins that adorn their outer surface, which resemble a crown (corona) under a microscope. As a family, they infect a wide range of animals, including humans.

[...] SARS-CoV-2 is related to coronaviruses in bats, but its intermediate animal host and route to humans are not yet clear. There has been plenty of speculation that the intermediate host could be pangolins, but that is not confirmed.

While the identity of SARS-CoV-2's intermediate host remains unknown, researchers suspect the mystery animal was present in a live animal market in Wuhan, China—the capital city of China's central Hubei Province and the epicenter of the outbreak. The market, which was later described in Chinese state media reports as "filthy and messy," sold a wide range of seafood and live animals, some wild. Many of the initial SARS-CoV-2 infections were linked to the market; in fact, many early cases were in people who worked there.

[...] That said, a report in The Lancet describing 41 early cases in the outbreak indicates that the earliest identified person sickened with SARS-CoV-2 had no links to the market. As Ars has reported before, the case was in a man whose infection began causing symptoms on December 1, 2019. None of the man's family became ill, and he had no ties to any of the other cases in the outbreak.

[...] In people, SARS-CoV-2 causes a disease dubbed COVID-19 by the World Health Organization (WHO). As the US Centers for Disease Control and Prevention (CDC) points out, the 'CO' stands for 'corona,' 'VI' for 'virus,' and 'D' for disease. [...] On average, it takes five to six days from the day you are infected with SARS-CoV-2 until you develop symptoms of COVID-19. This pre-symptomatic period—also known as "incubation"—can range from one to 14 days.

From there, those with mild disease tend to recover in about two weeks, while those with more severe cases can take three to six weeks to recover, according to WHO Director-General Dr. Tedros Adhanom Ghebreyesus, who goes by Dr. Tedros.

[...] So far, some preliminary population screening for COVID-19 infections has been done in China, specifically in Guangdong province. Screening of 320,000 people who went to a fever clinic suggested that we may not be missing a vast number of mild cases. This in turn suggests that the CFRs we are calculating now are not wildly higher than they should be. However, experts still suspect that many mild cases are going unreported, and many still anticipate that the true CFR will be lower than what we are calculating now.

Hodcroft decided to generate an infographic showing the connections between the traveler from Singapore and the other coronavirus cases emerging in Europe. "I thought, I'll make an image and see if anyone else finds this useful," she says. She posted the image on Twitter, and "somewhat unexpectedly, it got a lot of attention," she says. "People were definitely really, really interested in this. So I kept that image updated over the next week or so." As she updated it, the graphic showed that at least 21 people were exposed to the virus at the ski resort the traveler from Singapore visited; 13 of those people ended up developing COVID-19, the disease caused by the virus. After she'd finished the preliminary work, a colleague of Hodcroft saw it and suggested she write it up for publication. She posted the paper on February 26; the next day it appeared in Swiss Medical Weekly.

Hodcroft talked with The Scientist about the work, how its conclusions have been supported by genetic testing of viral strains from patients, and what it tells us about the spread of the virus, SARS-CoV-2, in other countries.

The other thing that's surprising is that, according to the patient statement that he released, the focal patient never had any symptoms. In his own words, he never felt sick. So he did all of this transmission without ever having any indication that he was unwell or that he should be taking any precautions to modify his behavior. It tells us that some infections might be from people who never even know that they're sick.

A few days ago, the research group called the Seattle Flu Study, which is designed to take community samples from random people who have any kind of cough, runny nose, or cold-like symptoms and look for the flu—they pivoted and started testing some of the samples for coronavirus. They found a case in the Seattle area and sequenced the viral genome of the infected person [posted on NextStrain] and showed it links very closely with another case in the Seattle area that's from mid-January. And so this strongly suggests (though we don't yet know for certain) that there has been ongoing undetected transmission in Seattle since mid-January and wasn't picked up because we weren't looking for it. This has become clearer in the last few days, as more cases and even deaths have been reported in Washington State. That tells us the virus hasn't just appeared in the last few days in the area.

When you have a very small number of cases of a disease, you can do this just through epidemiological contact tracing: you can go to everyone and ask questions and find out the connections between the cases. As the case numbers scale up, this becomes very hard to do. With genetic sequencing, we can do this without having to go and try and figure out where everyone was at the time of infection. We've had an influx of sequences from Brazil, Switzerland, Mexico, Scotland, Germany. These have clustered with sequences from Italy and have a travel history from Italy and so from that we can show that Italy really is now exporting cases around the world to multiple countries.

One thing I would note is that studies have shown that limiting transportation really doesn't make much of an impact for outbreaks. Quarantining particular cities, if they seem to be epicenters, can work as a preventive measure, but as the epidemic scales up, you move past being able to contain it in this sense, [and] what you end up doing is just disrupting supply routes, interrupting business, making all of these things much harder.

The secondary effects of the coronavirus are being felt around the world as factory production is slower, deliveries are affected and entire countries are shut down. In Australia the University of Tasmania is cutting courses in a bid to survive foreign student loss in the midst of a travel ban imposed by Australia in a bid to slow the coming COVID19 outbreak. With UTAS (University of Tasmania) buying up tens of millions worth of real estate in prime areas for future expansion based on foreign students the future of the university may be in doubt with so many of its wealthy students unable to attend. Given expectations that the virus outbreak is expected to last months, UTAS may have to suck in its belt, reduce courses, and ride out the wave like so many other businesses facing extinction. Already several restaurants in the Sydney Chinatown area have closed due to the ongoing situation with many more predicted to come.