CORONAVIRUS SARS-COV-2 – BIOLOGY, DETECTION AND TREATMENT
The coronavirus pandemic is an unusual period for all of us. We are facing the fear and uncertainty about our and our close ones’ health, about the job and the future. Some of us are facing loss of our loved ones. We had to change our daily routines, reorganise our work, learning and looking after children. We do not know when everything will come back to normal or whether this “normal” that we used to know will ever come back. We are not able to predict how the situation will develop.
In these difficult times, we have asked the scientists from the University of Wrocław to share with us how they look at the situation from their scientific perspective. For starters, Prof. Zuzanna Drulis-Kawa from the Institute of Genetics and Microbiology will tell us what the coronavirus is.
SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is a virus causing acute respiratory distress syndrome, which was called COVID-19 (Coronavirus Disease-19). The first cases of infection with this virus were reported in December 2019 in China. In January 2020, the disease started to spread across the Mainland China, with the epicentre in the Wuhan city (Zhou et al. 2020). Shortly, it turned out that the SARS-CoV-2 virus was highly infectious. People started to infect one another through droplet transmission and, consequently, the virus was “taken” to the other parts of the world. Just after two months after the outbreak in Wuhan, COVID-19 reached the size of a pandemic, which was announced by the WHO (World Health Organisation) on 11 March 2020.
SARS-Cov-2 is the seventh virus from the coronaviruses family that infect people. In this group, there are also SARS-CoV, which caused the epidemic in 2002-2003, and MERS-CoV, which was responsible for an acute infectious disease known as the Middle East Respiratory Syndrome, described for the first time in 2012. Other viruses from this group are responsible for mild respiratory tract infections in people and animals ((Zhou et al. 2020; Andersen et al. 2020).
SARS-CoV-2 is a tunicary virus whose genome constitutes single-stranded RNA with a positive polarity and consisting of 29 903 nucleoids, which makes it one of the biggest RNA viruses. The characteristic feature is its “crown,” built with S-glycoprotein, that allows the virus to enter the cells.
Coronaviruses show tropism to epithelial cells of the respiratory and digestive system. The receptor that SARS-VoV-2 particles bind to is the ACE2 protein (angiotensin-converting enzyme II) that is present both in humans and bats and that, among others, regulates the blood pressure and arterial spasms (Zhou et al. 2020). Recent research published in ‘Antiviral Research’ (Sigrist et al. 2020) suggests that SARS-CoV-2 might also use other receptors (integrins) to attach to our cells. That is due to the unique structure of its glycoprotein (S), which differs from the corresponding structures in other coronaviruses. That unique structure of SARS-CoV-2 may potentially lead to the extension of its tropism to different target-cells and increase of the pathogen’s virulence (Sigrist et al. 2020). Interestingly enough, the strategy of binding to the integrins is common in other human viruses, not related to SARS-CoV-2, such as andenoviruses, rotaviruses, or cytomegaloviruses. In the genetic analysis of SARS-CoV-2 conducted by Andersen’s team (Andersen et al. 2020), it was concluded that the virus was not made in a lab. It turned out that the protein is similar to the proteins of the human virus SARS-CoV, as well as to bat and Malayan pangolin viruses (Andersen et al. 2020). However, there are significant differences that might probably increase the virulence of SARS-CoV-2. The appearance of additional elements in the S-glycoprotein sequence, such as ‘O-linked glycans,’ led to the easier transmission from person to person. A similar relationship was observed in an earlier research on the avian flu, which analogically acquired the ability to infect and spread among humans. The above-mentioned modifications in the surface structure of the S-glycoprotein, may potentially increase the infectiousness of the SARS-CoV-2 virus.
So far, the exact origins of the SARS-CoV-2 virus is unknown. However, 80% resemblance to the SARS-CoV that caused the disease in 2002-2003 suggests that both viruses probably originated in the same natural reservoir, which are bats (Zhou et al. 2020).
Following the current WHO recommendations regarding the diagnosis of SARS-CoV-2, we apply the “real-time RT-PCR” method to detect the genetic material of the virus that was gathered from the upper and lower respiratory tracts of a patient in test tubes. That method is highly sensitive and specific due to detecting the nucleic acid sequence that is specific to SARS-CoV-2. Theoretically, it is feasible to detect fragments of the virus in the gathered samples with the use of marked monoclonal antibodies. In that case, the processing and analysis would be less time-consuming than in the “real-time RT-PCR” method. Nonetheless, devising such tests requires time and standardisation of a new methodology.
Another approach in infection diagnosis are serological methods that are based on detecting specific antibodies from the human serum. These antibodies are developed in human body as a response to an infection. As COVID-19 is a new disease, there is yet no sufficient data that would enable us to establish standards for interpreting the serological tests. Furthermore, detecting antibodies in an early phase of infection may give a negative result because the body might have not developed the sufficient number of specific antibodies.
Treatment of viral infections is not an easy task due to the variety of viruses and their strategies of proliferating in our cells. At our disposal, there are a few therapeutic variants, such as using micro-molecular chemical compounds, peptide and oligonucleotide therapy, therapies based on interferon and monoclonal antibodies. The group of coronaviruses is well known in terms of mechanisms of propagation. Therefore, knowledge gained during the SARS epidemic in 2002 allows us to use the drugs already approved for human treatment (Guangdi, De Clercq 2020; Wang et al. 2020).
There are several medicines that are deemed effective. The first one is chloroquine, which is used effectively as an antimalarial drug, as well as in treatment of autoimmunological diseases, such as rheumatoid arthritis or lupus.
The next group are drugs used for treating the infection caused by retroviruses, including HIV, that are based on compounds that inhibit development of newly created viral particles. In this group, the drugs that are approved for therapy are Lopinavir (Kaletra) and Ritonavir (Norvir, Ritonavir).
Remdesivir, which was developed by Gilead Sciences Inc., belongs to the third group of drugs. Currently, it is under clinical trials and it achieved success in ebola virus treatment. Its effectiveness in the treatment of infections caused by the coronaviruses MERS-CoV and SARS-CoV was confirmed during testing in animals. Remdesivir is an analogue of adenosine and it inhibits replication of the genetic material of the virus.
The fourth type of therapy that is used for coronaviruses infections employs drugs that are still on the drawing board. They block the main enzyme of SARS-CoV-2 (M-protease) that is crucial for developing functional protein of the virus. Study on the inhibitors of this enzyme, based on the structural analysis of the protein, is conducted by the team led by Prof. Marcin Drąg from the Wrocław University of Science and Technology, in cooperation with a team led by Prof. Rolf Hilgenfeld from the University of Lübeck (Zhang et al. 2020; Rut et al. 2020).
The basic way of preventing a society from infectious diseases is vaccination. Its aim is to protect against a disease both those vaccinated and, by developing so called “herd immunity,” those not vaccinated. At the moment, there are several types of vaccines used for viral and bacterial infections. There are live vaccines that contain virulence-free micro-germs. The second type are vaccines containing dead pathogens. The third one are recombinant vaccines that contain chosen elements of a micro-germ that are developed with methods of molecular biology. These vaccines have only selected antigens of a pathogen whose aim is immunisation of patients. Currently, studies on the development of an effective and safe vaccine against the SARS-CoV-2 virus are being conducted in the whole world.
A few days ago, the American National Institutes of Health announced launching the first phase of a clinical trial on the novel vaccine mRNA-1273, which is based on a portion of the genetic material of the SARS-CoV-2 virus (https://www.nih.gov/news-events/news-releases/nih-clinical-trial-investigational-vaccine-covid-19-begins). The mRNA-1273 vaccine was developed by the scientists from the National Institute of Allergy and Infectious Diseases (NIAID) in collaboration with Miderna Inc., a biotechnological company based in Cambridge, Massachusetts. In the study conducted at the Kaiser Permanente Washington Health Research Institute in Seatle, there participated 45 healthy volunteers from the age between 18 and 55. They will be vaccinated and then monitored for 12 months in order to assess the safety and immunogenicity.
The most up-to-date information on the development of the COVID-19 pandemic, research being conducted, statistics, epidemiological and diagnostic recommendations, treatment and prevention, is to be found on the WHO website (https://www.who.int/emergencies/diseases/novel-coronavirus-2019).
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Guangdi, L., De Clercq, E. (2020). Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nature Review Drug Discovery [doi.org/10.1038/d41573-020-00016-0].
Rut, W., et al. (2020). Substrate specificity profiling of SARS-CoV-2 Mpro protease provides basis for anti-COVID-19 drug design. bioRxiv preprint [doi.org/10.1101/2020.03.07.981928].
Sigrist, Ch.J.A., Bridge, A., Le Mercier, Ph. (2020). A potential role for integrins in host cell entry by SARS-CoV-2. Antiviral Research, 177, 104759 [doi.org/10.1016/j.antiviral.2020.104759].
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Prof. Zuzanna Drulis-Kawa