Lit up

Biosensor recognizes coronavirus mutations

The device will assess the degree of contagion of new strains of SARS-CoV-2 and help to find a cure for them

Olga Kolentsova, Izvestia

Foreign scientists have developed a biosensor that will help assess the level of contagion of some new SARS-CoV-2 mutations. The device evaluates the interaction of the coronavirus spike and the ACE2 enzyme through which it enters the body. Scientists attach one fragment of the luciferase protein to the spike, and another to the enzyme. When the two components are combined, luciferase glows. This technique will help to analyze the ability of viruses with new mutations to penetrate the cell, as well as to evaluate the effectiveness of drugs, experts say. But so far, it turns out to conduct such experiments only under ideal conditions, that is, in a test tube.

With the help of fireflies

Scientists from Queens University and the University of British Columbia (Canada) A biosensor was created to assess the interaction of the coronavirus with the cells through which it enters the body. The prototype of the device helps to quantify how actively a special protein on the coronavirus binds to the ACE2 enzyme in the infected cells.

Article by Yang et al. An Ultrasensitive Biosensor for Quantifying the Interaction of SARS-CoV-2 and Its Receptor ACE2 in Cells and in vitro is published on the bioRxiv website.

There is a spike-like protein (S) on the surface of SARS-CoV-2. It allows the coronavirus to attach to the receptor of a human cell at the moment of penetration into it. This spike is often called a key, which is inserted into the lock on the surface of the cage. Lock is an ACE2 enzyme that is present in most body tissues.

In order for the biosensor to show the result, the scientists decided to use the luminous enzyme luciferase (it also works in fireflies). Scientists have divided this protein into two parts. One was attached to a coronavirus spike, and the other to ACE2. Separately, the parts of the protein do not glow, but when combined they begin to do so. By the intensity of the light, you can estimate how many spikes have associated with ACE2. The analysis takes half an hour, the scientists said.

The device can be used, for example, to evaluate the effectiveness of drugs against SARS-CoV-2. If the drug to block the spike of the virus works, then the system will not emit light, because the luciferase fragments will not connect. In addition, it is possible to indirectly assess the contagiousness of a new strain of coronavirus if the mutation affected the thorn.

"This simple and fast biosensor will significantly accelerate the detection of viral mutants and the processes of drug discovery against COVID-19," the authors of the invention summed up.

Works clean

The biosensor can be used in fundamental research, but there are doubts about its practical use, Russian experts say.

— So far, we are talking only about the registration of the luminescent effect during the interaction of SARS-CoV-2 and ACE2 in ideal, "clean" conditions, — Sergey Kudryashov, a leading researcher at the Faculty of Laser Photonics and Optoelectronics at ITMO University (the university is a participant in the project to increase the competitiveness of education "5-100"), told Izvestia. — For example, in order to evaluate the work of the sensor to assess the action of antibodies against coronavirus, additional antibody isolation procedures will be required. The path to practical application can be both short and endless.

Attaching a luciferase fragment not only to a thorn, but to the whole SARS-CoV-2 virus is a much more difficult task, Roman Zinovkin, a leading researcher at the Laboratory of Molecular Biology at Lomonosov Moscow State University, drew attention. Thus, the operation of the device is limited to studying the interaction between two proteins. Nevertheless, this way it is possible to analyze the effectiveness of drugs or antibodies to "block" the virus, as well as how a specific mutation of the spike will facilitate the penetration of the virus into the cell or complicate it, the scientist believes.

— It is premature to talk about the use of the described biosensor in the clinical diagnosis of coronavirus infection, — said Andrey Vasin, acting director of the Institute of Biomedical Systems and Biotechnologies of Peter the Great St. Petersburg Polytechnic University. — It really has potential when used in vitro (in vitro. — "Izvestia") screening of candidate drugs against SARS-CoV-2 to assess their effectiveness. This approach is not applicable directly for the diagnosis of COVID-19 and the determination of SARS-CoV-2 as presented.

The potential of the sensor in clinical diagnostics and the creation of drugs from COVID-19, most likely, does not exist, according to Sergey Netesov, head of the Laboratory of Biotechnology and Virology of the Faculty of Natural Sciences of NSU, corresponding member of the Russian Academy of Sciences.

— The biosensor does not detect the presence of a single viral marker, — the expert noted. — When evaluating candidates for antiviral drugs, it is still necessary to conduct parallel studies of these drugs on model animals.

However, the method described by Canadian scientists has advantages.

— The method is designed to optimize the processes of creating antiviral drugs and is very useful because it accelerates the testing of the effectiveness of the compounds being developed, — said Tatiana Zimina, a leading researcher at the Engineering Center for Microtechnology and Diagnostics of SPbSETU "LETI". — "Classical" testing methods using live cultures require work in special conditions with sufficiently strict permits. The method of analysis of Canadian scientists can be used on fragments of the biosystem that do not belong to the class of hazardous substances and are more accessible in scientific laboratories.

The St. Petersburg State Electrotechnical University "LETI", in cooperation with the A.A. Smorodintsev Influenza Institute, is also working on the design of reagents that block the interaction of the coronavirus spike and the receptor. At the time of publication, Rospotrebnadzor did not respond to a request from Izvestia about similar methods being developed in Russia.

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