Stop Covid with CRISPR Diagnostics (2)

CRISPR–Cas12-based detection of SARS-CoV-2

Mammoth Biosciences (a firm founded by Jennifer Doudna) has partenered with GSK to commercialise a CRISPR Covid test. Therefore, there are right now two firms in the race: Sherlock and Mammoth.
The paper in Nature explains the details:

Here we report the development and initial validation of a CRISPR–Cas12-based assay9 for detection of SARS-CoV-2 from extracted patient sample RNA, called SARS-CoV-2 DNA Endonuclease-Targeted CRISPR Trans Reporter (DETECTR). This assay performs simultaneous reverse transcription and isothermal amplification using loop-mediated amplification (RT–LAMP)14 for RNA extracted from nasopharyngeal or oropharyngeal swabs in universal transport medium (UTM), followed by Cas12 detection of predefined coronavirus sequences, after which cleavage of a reporter molecule confirms detection of the virus. We first designed primers targeting the E (envelope) and N (nucleoprotein) genes of SARS-CoV-2 (Fig. 1a). The primers amplify regions that overlap the World Health Organization (WHO) assay (E gene region) and US CDC assay (N2 region in the N gene)6,15, but are modified to meet design requirements for LAMP. We did not target the N1 and N3 regions used by the US CDC assay, as these regions lacked suitable protospacer adjacent motif sites for the Cas12 guide RNAs (gRNAs). Next, we designed Cas12 gRNAs to detect three SARS-like coronaviruses (SARS-CoV-2 (accession NC_045512), bat SARS-like coronavirus (bat-SL-CoVZC45, accession MG772933) and SARS-CoV (accession NC_004718)) in the E gene and specifically detect only SARS-CoV-2 in the N gene (Supplementary Fig. 1). This design is similar to those used by the WHO and US CDC assays, which use multiple amplicons with probes that are either specific to SARS-CoV-2 or are capable of identifying related SARS-like coronaviruses.

Edward Hopper 

After all these years, a new pandemic and the same behavioral biases

Using social and behavioural science to support COVID-19 pandemic response

This is the best paper as far as I know on behavioral biases in the current pandemic. The conclusion says:

Over 100 years ago, Science magazine published a paper on lessons from the Spanish Flu pandemic. The paper argued that three main factors stand in the way of prevention: (i) people do not appreciate the risks they run, (ii) it goes against human nature for people to shut themselves up in rigid isolation as a means of protecting others, and (iii) people often unconsciously act as a continuing danger to themselves and others. Our paper provides some insights from the past century of work on related issues in the social and behavioural sciences that may help public health officials mitigate the impact of the current pandemic. Specifically, we discussed research on threat perception, social context, science communication, aligning individual and collective interests, leadership, and stress and coping. 

A century ago paper:  Soper, G. A. The lessons of the pandemic. Science 49, 501–506 (1919).

First, public indifference. People do not appreciate the risks they run. The great complexity and range in severity of the respiratory infections confuse and hide the danger. The infections vary from the common cold to pneumonia. They are not all separate entities by any means. An attack which begins as a coryza or rhinitis may develop into a pharyngitis, tonsilitis, laryngitis, bronchitis or pneumonia. The gravity increases with the progress toward the lungs. The infection sometimes seems to begin in the chest, sometimes in the throat, sometimes in the head. It may stop where it started or pass through several phases. This is the story of the common cold. It is generally more discomforting than dangerous. Most people get well without skillful treatment, or indeed any great interference with business. No specific virus is known to produce it.

Searching for a vaccine and a drug in the surreal and accelerated world of Covid-19 research

What Is the World Doing to Create a COVID-19 Vaccine?

Building the critical path for COVID-19 therapeutics

How to Discover Antiviral Drugs Quickly

The world needs Covid-19 vaccines. It may also be overestimating their power

From CFR:

Public officials worldwide have stressed that the pandemic likely will not end until there is an effective vaccine. Even after a vaccine is approved, however, there remains the tremendous challenge of producing enough of it for the world’s population. An estimated one billion doses would need to be manufactured just to vaccinate workers in health care and other essential industries globally, and that is if only a single dose is required for each person.
This task has both motivated countries to prepare for large-scale production, as well as pitted them against one another amid fears of a potentially limited vaccine supply. While Brazil, China, and India all have large vaccine industries, they also have among the largest populations, and they could reserve their vaccine supplies for their own citizens before opening them up to others. Some countries are seeking to strike monopoly agreements with vaccine manufacturers to avoid domestic shortages. Experts including CFR’s Bollyky have warned that bidding wars over a vaccine will lead to inequitable distribution and, ultimately, fail to eliminate the risk of new outbreaks.
Moreover, amid these extraordinary efforts to secure a vaccine, scientists are still investigating how this new coronavirus behaves and trying to answer the many questions people have about the risk it poses and how protected they will be. This includes how effective a vaccine will be against a mutating coronavirus, though researchers point out that mutations do not necessarily mean different strains of the virus or changes in its infectiousness or lethality. Uncovering such details about the virus, they say, will only help in the development of a successful vaccine.

From NEJM:

 So, what is happening now? The laborious, decade-long, classic pathway for the discovery and approval of new drugs could hardly be less well suited to the present pandemic. Repurposing existing drugs offers a potentially rapid mechanism to deployment, since the safety profiles are known. Therefore, a preliminary report of a supercomputer-driven ensemble docking study of a repurposing compound database to the viral S protein was published on a preprint server in mid-February, with 8000 compounds ranked according to the calculated binding affinity to the receptor-binding domain of the S protein.3 Top-ranked compounds from the original S-protein virtual screen are being tested for activity against the live virus. The results will inform future calculations in a speedy, iterative process.

Counterfeit medicines: the time to act is now

Trade in Counterfeit Pharmaceutical Products
Coronavirus (COVID-19) and the global trade in fake pharmaceuticals

OECD has released an iluminating report about counterfeit medicines around the world. And my surprise was:

Commenting specifically on manufacturing, Table 4.5 indicates that China arrested the largest number of individuals engaged in the manufacture of counterfeit medicines. It was followed by Spain, the United States, India, Pakistan and Indonesia. Note that almost all of these countries (except the United States and Spain) were identified as potential producers of counterfeit pharmaceuticals in the methodology developed by OECD/EUIPO and described in the previous section .

The second method for determining the main producing economies of fake pharmaceuticals and the key transit points involves using PSI data. Through liaison   contacts, member reports and open source reports, PSI has documented the arrest of 2253 people involved in counterfeiting, diversion or theft of pharmaceutical drugs worldwide during 2018. 

Table 4.5. Top ten countries for the number of arrests of individuals engaged in manufacturing counterfeit medicines, 2018

Economy

Number of arrests

China

233

Spain

52

United States

48

India

38

Pakistan

10

Indonesia

10

Canada

7

Colombia

6

Egypt

1

Source: PSI data.

As you can see, Spain is the second country in the world. Nothing to add.

Can capitalism be reimagined? (2)

Capitalism at Risk: Rethinking the Role of Business

Ten years after its first release, a new and updated edition of this book is available. Let me say that the book by Rebecca Henderson is better than this one. Anyway, this is an additional reference to take into account.

WHAT, THEN, should be done about the challenges facing market capitalism? And what, specifically, is the role of business in this effort? In our conversations, we heard answers reflecting a spectrum of views. Although executives in our forums did not use our terminology, their positions clustered into four broad categories that we term business as bystander, business as activist, business as innovator, and business as usual.

Ten years after, the same views...(?)

Assessing the government job on COVID-19

The citizens voice has said that several governments are doing a poor job in front of covid-19. Japan, Spain and France are the worst.  In the case of Spain there are clear reasons behind such opinion (please see below).

A picture is worth a thousand words

Germline editing: fasten seat belts

The Case for Remedial Germline Editing—The Long-term View

We conclude that so long as heritable genome editing interventions are consistent with the welfare of the future person and with social justice and solidarity, they do not contravene any categorical moral prohibition.
Nuffield Council on Bioethics (2018)

This statement changed the existing bioethics view on genome editing. From then, the door is open and nobody knows exactly what does it mean.

In this article, the authors open the possibilities without knowing exactly its implications:

 Two technologies under consideration to tackle this challenge are preimplantation genetic diagnosis (PGD) and remedial germline editing (RGE). Preimplantation genetic diagnosis is an established diagnostic technique, widely deployed today to identify a genetic defect in embryos created through in vitro fertilization, with the goal of transferring only embryos lacking the defect to the mother’s uterus. Remedial germline editing is a novel therapeutic paradigm that has has yet to be applied in the clinic to correct a heritable deleterious mutation in a fertilized egg. We predict that, in time, safe and efficacious RGE will eclipse PGD, the relative shortcomings of which are becoming increasingly apparent.

The final reports of the International Commission on the Clinical Use of Human Germline Genome Editing and the World Health Organization’s Expert Advisory Committee on Developing Global Standards for Governance and Oversight of Human Genome Editing are due later this year.
Meanwhile, take care!