Robust detection of SARS-CoV-2 exposure in population using T-cell repertoire profiling (preprint)

The COVID-19 pandemic clearly demonstrates the need to monitor the spread of infectious diseases and population immunity. Probing adaptive immunity by sequencing the repertoire of antigen receptors (Rep-Seq) encoding specificity and immunological memory has become a method of choice for immunology studies. Rep-Seq can detect the imprint of past and ongoing infections and study individual responses to SARS-CoV-2 as shown in a number of recent studies. Here we apply a machine learning approach to two large datasets with more than 1200 high-quality repertoires from healthy and COVID-19-convalescent donor repertoires to infer T-cell receptor (TCR) repertoire features that were induced by SARS-CoV-2 exposure. Proper standardization of Rep-Seq batches, access to human leukocyte antigen (HLA) typing and both - and {beta}-chain sequences of TCRs allowed us to generate a high-quality biomarker database and build a robust and highly accurate classifier for COVID-19 exposure applicable to individual TCR repertoires obtained using different protocols, paving a way to Rep-Seq-based immune status assessment in large cohorts of donors.

In-Hospital Rehabilitation of Patients with COVID-19: A Retrospective Study with Propensity Score Matching (preprint)

Background: Early rehabilitation is an important strategy for the treatment of severe diseases. The study aimed to assess the efficacy of early rehabilitation of patients with mild-to-moderate COVID-19. Methods: The retrospective single-center study with propensity score matching. Results: 180 patients (54 (44 - 62.3) yo) divided into three equal groups: 1 - physical exercises; 2 - physical exercises and chest massage in an electrostatic field; 3 - no rehabilitation. The length of stay (LOS) in the hospital in group 1 was 14 (11-15) days, group 2 - 13 (11-15) days, group 3 - 15 (13-18) days, p=0.0026. Physical exercises for patients with CT-1 improved the quality of life, assessed by the EQ-5D questionnaire, by reducing the level of anxiety and depression. The Hazard Ratio (HR) for desaturation (<93%) was 2.34 (95% Confidence Interval (CI) 1.18-4.63) for group 2, p=0.001. The HR for C-reactive protein level above 50 mg/l in patients with CT-2 was 2.33 (95% CI 1.56-3.47), p=0.0001. Conclusions: Rehabilitation programs are safe for СOVID-19-patients; reduce hospital LOS; improve the quality of life. Continuous monitoring of a patient's condition during rehabilitation is essential. ClinicalTrials.gov ID: NCT0580836

Genomic epidemiology of SARS-CoV-2 in Russia reveals recurring cross-border transmission throughout 2020.

In 2020, SARS-CoV-2 has spread rapidly across the globe, with most nations failing to prevent or substantially delay its introduction. While many countries have imposed some limitations on trans-border passenger traffic, the effect of these measures on the global spread of COVID-19 strains remains unclear. Here, we report an analysis of 3206 whole-genome sequences of SARS-CoV-2 samples from 78 regions of Russia covering the period before the spread of variants of concern (between March and November 2020). We describe recurring imports of multiple COVID-19 strains into Russia throughout this period, giving rise to 457 uniquely Russian transmission lineages, as well as repeated cross-border transmissions of local circulating variants out of Russia. While the phylogenetically inferred rate of cross-border transmissions was somewhat reduced during the period of the most stringent border closure, it still remained high, with multiple inferred imports that each led to detectable spread within the country. These results indicate that partial border closure has had little effect on trans-border transmission of variants, which helps explain the rapid global spread of newly arising SARS-CoV-2 variants throughout the pandemic.

CLINICAL OUTCOMES IN PATIENTS WITH COVID-19 AND HEMATOLOGIC DISEASE

Background Patients with hematologic diseases are at higher risk of the SARS-CoV-2 infection and more severe clinical outcomes of the coronavirus disease. CHRONOS19 is an observational prospective cohort study with the aim to determine the short and longer-term clinical outcomes, risk factors for disease severity and mortality, and rates of postinfectious immunity in patients with malignant and non-malignant hematologic diseases and COVID-19. Patients and Methods : Overall, 666 patients were enrolled in the study, of which 626 were included in the final data analysis. The primary endpoint was 30-day all-cause mortality. Secondary endpoints included COVID-19 complications, rates of ICU admission and mechanical ventilation, outcomes of a hematologic disease in SARS-CoV-2 infected patients, overall survival, and risk factors for disease severity and mortality. Data from 15 centers were collected at 30, 90, and 180 days after COVID-19 was diagnosed and were managed using a web-based e-data capture platform. All evaluations were performed in the pre-omicron period of COVID-19 pandemic. Results Thirty-day all-cause mortality was 18.9%. The predominant cause of death (in 80% of cases) were COVID-19 complications. At 180 days, the majority (70%) of additional deaths were due to hematologic disease progression. At a median follow-up of 5.7 [0.03-19.04] months, 6-month overall survival was 72% [95% CI: 0.69-0.76]. One-third of patients had severe SARS-CoV-2 disease. The rate of ICU admission was 22% with 77% of these patients requiring mechanical ventilation, with poor survival rate. A univariate analysis revealed that older age (≥ 60 years), male sex, malignant hematologic disease, myelotoxic agranulocytosis, transfusion dependence, refractory disease or relapse, diabetes among comorbidities, any complications, especially ARDS alone or in combination with CRS, admission to an ICU, and mechanical ventilation were associated with higher risks of mortality. Treatment of the hematologic disease was changed, postponed, or canceled in 63% of patients. At a longer follow-up (90 and 180 days), the status of the hematologic disease changed in 7.5% of patients. Conclusion Patients with hematologic disease and COVID-19 have high mortality rates, predominantly due to COVID-19 complications. At a longer-term follow-up, no significant impact of COVID-19 on the course of a hematologic disease was revealed. Micro Patients with hematologic conditions are at a higher risk of mortality due to COVID-19 compared to the general population. Further research and implementation of appropriate interventions in order to prevent the spread of the SARS-CoV-2 infection in this vulnerable patient population are warranted.

Biological Age Predictors: The Status Quo and Future Trends.

There is no single universal biomarker yet to estimate overall health status and longevity prospects. Moreover, a consensual approach to the very concept of aging and the means of its assessment are yet to be developed. Markers of aging could facilitate effective health control, more accurate life expectancy estimates, and improved health and quality of life. Clinicians routinely use several indicators that could be biomarkers of aging. Duly validated in a large cohort, models based on a combination of these markers could provide a highly accurate assessment of biological age and the pace of aging. Biological aging is a complex characteristic of chronological age (usually), health-to-age concordance, and medically estimated life expectancy. This study is a review of the most promising techniques that could soon be used in routine clinical practice. Two main selection criteria were applied: a sufficient sample size and reliability based on validation. The selected biological age calculators were grouped according to the type of biomarker used: (1) standard clinical and laboratory markers; (2) molecular markers; and (3) epigenetic markers. The most accurate were the calculators, which factored in a variety of biomarkers. Despite their demonstrated effectiveness, most of them require further improvement and cannot yet be considered for use in standard clinical practice. To illustrate their clinical application, we reviewed their use during the COVID-19 pandemic.

Mortality and survival in nonagenarians during the COVID-19 pandemic: Unstable equilibrium of aging

Introduction Aging puts the human body under an immense stress and makes it extremely susceptible to many diseases, often leading to poor outcomes and even death. Long-living individuals represent a unique group of people who withstood the stress of time and offer an abundance of information on the body's ability to endure the pressure of aging. In this study, we sought to identify predictors of overall one-year mortality in 1641 long-living individuals. Additionally, we analyzed risk factors for COVID-19-related morality, since statistics demonstrated an extreme vulnerability of older adults. Methods We conducted a two-stage evaluation, including a comprehensive geriatric assessment for major aging-associated: frailty, cognitive impairment, frontal lobe dysfunction, chronic pain, anxiety, risk of falls, sensory deficit, depression, sarcopenia, risk of malnutrition, fecal and urinary incontinence, dependence in Activities of Daily Living, dependence in Instrumental Activities of Daily Living, polypragmasia, and orthostatic hypotension;extensive blood testing, a survey, and a one-year follow-up interview. Results The most reliable predictors of overall mortality were cognitive impairment, malnutrition, frailty, aging-associated diseases and blood markers indicating malnutrition-induced metabolic dysfunctions (decreased levels of protein fractions, iron, 25-hydroxyvitamin D, and HDL), and aging biomarkers, such as IGF-1 and N-terminal pro b-type natriuretic peptide. In post-COVID 19 participants, the most significant mortality predictors among geriatric syndromes were depression, frontal lobe dysfunction and frailty, and similar to overall mortality blood biomarkers - 25-hydroxyvitamin D, IGF-1, HDL as well as high white blood cell, neutrophils counts and proinflammatory markers. Based on the results, we built a predictive model of overall mortality in the long-living individuals with f-score=0.76. Conclusion The most sensitive and reliable predictors of mortality were modifiable. This is another evidence of the critical importance of proper geriatric care and support for individuals in their "golden years”. These results could facilitate geriatric institutions in their pursuit for providing improved care and could aid physicians in detecting early signs of potentially deadly outcomes. Additionally, our findings could be used in developing day-to-day care guidelines, which would greatly improve prevention statistics.

Single-Cell Gene Expression Analysis Revealed Immune Cell Signatures of Delta COVID-19.

The coronavirus disease 2019 (COVID-19) is accompanied by a cytokine storm with the release of many proinflammatory factors and development of respiratory syndrome. Several SARS-CoV-2 lineages have been identified, and the Delta variant (B.1.617), linked with high mortality risk, has become dominant in many countries. Understanding the immune responses associated with COVID-19 lineages may therefore aid the development of therapeutic and diagnostic strategies. Multiple single-cell gene expression studies revealed innate and adaptive immunological factors and pathways correlated with COVID-19 severity. Additional investigations covering host-pathogen response characteristics for infection caused by different lineages are required. Here, we performed single-cell transcriptome profiling of blood mononuclear cells from the individuals with different severity of the COVID-19 and virus lineages to uncover variant specific molecular factors associated with immunity. We identified significant changes in lymphoid and myeloid cells. Our study highlights that an abundant population of monocytes with specific gene expression signatures accompanies Delta lineage of SARS-CoV-2 and contributes to COVID-19 pathogenesis inferring immune components for targeted therapy.

Model of the SARS-CoV-2 Virus for Development of a DNA-Modified, Surface-Enhanced Raman Spectroscopy Sensor with a Novel Hybrid Plasmonic Platform in Sandwich Mode.

The recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has posed a great challenge for the development of ultra-fast methods for virus identification based on sensor principles. We created a structure modeling surface and size of the SARS-CoV-2 virus and used it in comparison with the standard antigen SARS-CoV-2-the receptor-binding domain (RBD) of the S-protein of the envelope of the SARS-CoV-2 virus from the Wuhan strain-for the development of detection of coronaviruses using a DNA-modified, surface-enhanced Raman scattering (SERS)-based aptasensor in sandwich mode: a primary aptamer attached to the plasmonic surface-RBD-covered Ag nanoparticle-the Cy3-labeled secondary aptamer. Fabricated novel hybrid plasmonic structures based on "Ag mirror-SiO2-nanostructured Ag" demonstrate sensitivity for the detection of investigated analytes due to the combination of localized surface plasmons in nanostructured silver surface and the gap surface plasmons in a thin dielectric layer of SiO2 between silver layers. A specific SERS signal has been obtained from SERS-active compounds with RBD-specific DNA aptamers that selectively bind to the S protein of synthetic virion (dissociation constants of DNA-aptamer complexes with protein in the range of 10 nM). The purpose of the study is to systematically analyze the combination of components in an aptamer-based sandwich system. A developed virus size simulating silver particles adsorbed on an aptamer-coated sensor provided a signal different from free RBD. The data obtained are consistent with the theory of signal amplification depending on the distance of the active compound from the amplifying surface and the nature of such a compound. The ability to detect the target virus due to specific interaction with such DNA is quantitatively controlled by the degree of the quenching SERS signal from the labeled compound. Developed indicator sandwich-type systems demonstrate high stability. Such a platform does not require special permissions to work with viruses. Therefore, our approach creates the promising basis for fostering the practical application of ultra-fast, amplification-free methods for detecting coronaviruses based on SARS-CoV-2.

The Cross-Cultural Differences in Perceived Stress of the COVID-19 Pandemic in Schoolchildren from Russia and Kyrgyzstan With Normal and High Levels of Anxiety and Depression

Children and youth of school age form a special population group highly sensitive to various stressors and negative effects in everyday life. The COVID-19 pandemic crisis characterized by uncertainty, vulnerability, changes in quality of life together with urgent transition to distant/online learning affected significantly psychological well-being of children and youth. The aim of this study was to assess the cross-cultural differences in actual stress in Russian and Kyrgyz schoolchildren with high and low levels of anxiety and depression during the initial stage of the COVID-19 pandemic and after a year life during the pandemic. The descriptive cross-sectional study was conducted via an online survey completed by total 1834 schoolchildren aged from 13 to 18 from Russia and Kyrgyzstan, the periods of survey: 10th May-10th June, 2020;18th May-15th June, 2021. The Perceived Stress Scale and Hospital Anxiety and Depression Scale were used to assess stress, anxiety and depression scores. The findings suggest that there are cross-cultural differences in perceived stress amongst schoolchildren with high level of depression and anxiety: Russian respondents in 2021 demonstrated less pronounced index of the perceived stress than Kyrgyz schoolchildren. The stress level of Kyrgyz schoolchildren increased significantly in 2021 in comparison to the period of outbreak of the pandemic. In 2021 in both countries we found the same pattern: girls had significantly more pronounced stress than boys. The results disclose important aspects of the impact of COVID-19 on schoolchildren and demonstrate the emerging need of psychological aid and for supporting schoolchildren mental health. © 2022 by the authors.

Analyzing Successful Aging and Longevity: Risk Factors and Health Promoters in 2020 Older Adults.

Geriatric syndromes (GSs) and aging-associated diseases (AADs) are common side effects of aging. They are affecting the lives of millions of older adults and placing immense pressure on healthcare systems and economies worldwide. It is imperative to study the factors causing these conditions and develop a holistic framework for their management. The so-called long-lived individuals-people over the age of 90 who managed to retain much of their health and functionality-could be holding the key to understanding these factors and their health implications. We analyzed the health status and lifestyle of the long-lived individuals and identified risk factors for GSs. Family history greatly contributes to the health and prevention of cognitive decline in older adults. Lifestyle and certain socioeconomic factors such as education, the age of starting to work and retiring, job type and income level, physical activity, and hobby were also associated with certain GSs. Moreover, the levels of total protein, albumin, alpha-1 globulins, high-density lipoprotein, free triiodothyronine, and 25-hydroxyvitamin D were direct indicators of the current health status. The proposed mathematical model allows the prediction of successful aging based on family history, social and economic factors, and life-long physical activity (f1 score = 0.72, AUC = 0.68, precision = 0.83 and recall = 0.64).

Drug repurposing against SARS-CoV-2 using computational approaches.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has generated a critical need for treatments to reduce morbidity and mortality associated with this disease. However, traditional drug development takes many years, which is not practical solution given the current pandemic. Therefore, a viable option is to repurpose existing drugs. The structural data of several proteins vital for the virus became available shortly after the start of the pandemic. In this review, we discuss the importance of these targets and their available potential inhibitors predicted by the computational approaches. Among the hits identified by computational approaches, 35 candidates were suggested for further evaluation, among which ten drugs are in clinical trials (Phase III and IV) for treating Coronavirus 2019 (COVID-19).

Alternatives to Opioids for Acute Pain Management in the Emergency Department

* Since the opioid crisis is still present, if not worse, it is important for emergency physicians to avoid the use of opioids whenever possible. * Many alternatives exist. Nitrous oxide provides short-term analgesia and can be used in children as young as 1 year of age. * Sub-dissociative doses of ketamine can be used for acute pain relief. Slow infusion decreases the psychoperceptual effects commonly seen with ketamine. It may be of some use even in chronic pain. * Intravenous lidocaine had been recommended for acute pain, particularly due to renal colic. However, more recent studies suggest it is inferior to ketorolac. * The use of ultrasound-guided regional anesthesia has been increasing and has been shown to be of value in acute trauma, central line placement, renal colic, zoster, and chest tube placement.

Analysis of receptors responsible for the dysfunction of the human immune system by different viral infections (preprint)

There are difficulties in creating direct anti-viral drugs for all viruses, including new, suddenly arising infections, such as COVID-19. Therefore, pathogenetic therapy is often used to treat severe viral infections. Despite significant distinctions in the etiopathogenesis of viral diseases, they are often associated with the substantial dysfunction of the immune system. To identify shared mechanisms of immune dysfunction during infection by nine different viruses (cytomegalovirus, Ebstein-Barr virus, human T-cell leukemia virus type 1, Hepatitis B and C viruses, human immunodeficiency virus, Dengue virus, SARS-CoV, and SARS-CoV-2), we applied analysis of corresponding transcription profiles from peripheral blood mononuclear cells (PBMC). As a result, we revealed common pathways, cellular processes, and master regulators for studied viral infections. We found that all nine viral infections cause immune activation, exhaustion, cell proliferation disruption, and increased susceptibility to apoptosis. An application of network analysis allowed us to identify receptors of PBMC that are the proteins at the top of signaling pathways, which may be responsible for the observed transcription changes. The identified relationships between some of them and virus-induced immune disfunction are new, with little or no information in the literature, e.g., receptors for autocrine motility factor, insulin, prolactin, angiotensin II, and immunoglobulin epsilon.

Rhaponticum uniflorum and Serratula centauroides Extracts Attenuate Emotional Injury in Acute and Chronic Emotional Stress.

In modern life, the use of plant stress-protectors has taken on particular significance due to the wide distribution of neurosis-like and neurotic diseases caused by neuroendocrine-immune system imbalance. Special attention has been paid to the plants containing ecdysteroids, i.e., hormone-like bioactive substances with high adaptogenic activity. The article deals with the study of bioactivity of two plant extracts as Rhaponticum uniflorum (L.) DC. and Serratula centauroides L. with a high content of ecdysteroids and phenolic compounds. The models of acute and chronic emotional stress in white rats were used to estimate the stress-protective activity of R. uniflorum and S. centauroides extracts. Both extracts showed the stress-protective effect via inhibiting the development of signs induced by single and long-term effects of stress factors. In acute stress, the development of Selye's triad signs was less pronounced against the background of the plant remedies introduction. In chronic stress, the extracts prevented the development of anxiety-depressive syndrome. Besides, R. uniflorum and S. centauroides extracts banned the development of stress-induced injuries in the brain cortex and had a neuroprotective effect on ischemia against chronic stress. The stress-protective effects of both plant extracts were based on a decrease of hyperactivation of the central stress-promoting systems (sympathoadrenal, hypothalamic-pituitary-adrenal) due to their GABA-mimetic effects. Peripheral mechanisms were connected with the inhibition of free radical oxidation processes and with an increase in the endogenous antioxidant system activity. Thus, R. uniflorum and S. centauroides extracts have a high potential to increase non-specific body resistance against acute and chronic emotional stress effects.

Development and Validation of a Multivariable Risk Prediction Model for COVID-19 Mortality in the Southern United States.

OBJECTIVE: To evaluate clinical characteristics of patients admitted to the hospital with coronavirus disease 2019 (COVID-19) in Southern United States and development as well as validation of a mortality risk prediction model. PATIENTS AND METHODS: Southern Louisiana was an early hotspot during the pandemic, which provided a large collection of clinical data on inpatients with COVID-19. We designed a risk stratification model to assess the mortality risk for patients admitted to the hospital with COVID-19. Data from 1673 consecutive patients diagnosed with COVID-19 infection and hospitalized between March 1, 2020, and April 30, 2020, was used to create an 11-factor mortality risk model based on baseline comorbidity, organ injury, and laboratory results. The risk model was validated using a subsequent cohort of 2067 consecutive hospitalized patients admitted between June 1, 2020, and December 31, 2020. RESULTS: The resultant model has an area under the curve of 0.783 (95% CI, 0.76 to 0.81), with an optimal sensitivity of 0.74 and specificity of 0.69 for predicting mortality. Validation of this model in a subsequent cohort of 2067 consecutively hospitalized patients yielded comparable prognostic performance. CONCLUSION: We have developed an easy-to-use, robust model for systematically evaluating patients presenting to acute care settings with COVID-19 infection.

Tailoring the management of hypertension to comorbidities.

PURPOSE OF REVIEW: In this article, we review the most current evidence for initiation and maintenance of various antihypertension (HTN) drug classes, including other misconceptions with respect to common comorbidities in patients with HTN. RECENT FINDINGS: Although the currently available anti-HTN agents have broad applicability in treating HTN, additional agents, such as angiotensin receptor-neprilysin inhibitors and novel nonsteroidal mineralocorticoid antagonists, have recently gained clinical significance. In addition, there have been some anecdotal concerns regarding the adverse effects, indications, and risks of COVID-19 infection/mortality when using certain anti-HTN agents. SUMMARY: Current guidelines currently address the treatment of primary HTN. However, isolated HTN is uncommon and often involves comorbid diseases that require specific regimentation. Several experimental medications are currently in late-stage trials showing potential superiority over current drugs that are available in the market.

Genomic epidemiology of SARS-CoV-2 in Russia reveals recurring cross-border transmission throughout 2020 (preprint)

SARS-CoV-2 has spread rapidly across the globe, with most nations failing to prevent or substantially delay its introduction. While many countries have imposed some limitations on trans-border passenger traffic, the effect of these measures on the spread of COVID-19 strains remains unclear. Here, we report an analysis of whole-genome sequencing of 3206 SARS-CoV-2 samples from 78 regions of Russia covering the period between March and November 2020. We describe recurring imports of multiple COVID-19 strains throughout this period, giving rise to 457 uniquely Russian transmission lineages, as well as repeated cross-border transmissions of local circulating variants out of Russia.

Thymulin and peroxiredoxin 6 have protective effects against streptozotocin-induced type 1 diabetes in mice.

Protective effects of peroxiredoxin 6 (PRDX6) in RIN-m5F ß-cells and of thymulin in mice with alloxan-induced diabetes were recently reported. The present work was aimed at studying the efficiency of thymulin and PRDX6 in a type 1 diabetes mellitus model induced by streptozotocin in mice. Effects of prolonged treatment with PRDX6 or thymic peptide thymulin on diabetes development were evaluated. We assessed the effects of the drugs on the physiological status of diabetic mice by measuring blood glucose, body weight, and cell counts in several organs, as well as effects of thymulin and PRDX6 on the immune status of diabetic mice measuring concentrations of pro-inflammatory cytokines in blood plasma (TNF-α, interleukin-5 and 17, and interferon-γ), activity of NF-κB and JNK pathways, and Hsp90α expression in immune cells. Both thymulin and PRDX6 reduced the physiological impairments in diabetic mice at various levels. Thymulin and PRDX6 provide beneficial effects in the model of diabetes via very different mechanisms. Taken together, the results of our study indicated that the thymic peptide and the antioxidant enzyme have anti-inflammatory functions. As increasing evidences show diabetes mellitus as a distinct comorbidity leading to acute respiratory distress syndrome and increased mortality in patients with COVID-19 having cytokine storm, thymulin, and PRDX6 might serve as a supporting anti-inflammatory treatment in the therapy of COVID 19 in diabetic patients.

Promising compounds from natural sources against COVID-19

The epidemic associated with the new Sars-CoV-2 coronavirus has affected almost all countries of the world and no reliable treatment for this infection exists yet. Many laboratories in the world are currently conducting intensive experimental and theoretical/in silico studies to find effective drugs specific for this disease (COVID-19), but unfortunately, it may take a long time before new drugs appear in the clinical practice. One of the currently widely accepted approaches for finding active compounds is based on the possibility of using existing drugs approved by government medical organizations (as the FDA). Their choice is based on screening, based on the use of computer models that evaluate the specific binding (energy minimization) of such drugs to target molecules that are important for the life cycle. Thus, a few well-known antiviral drugs against HIV, hepatitis C and others selected on this basis exerted an antiviral effect in vitro, but their real effectiveness was far from expected. It should be emphasized that the severe clinical manifestation of the disease is an acute respiratory distress syndrome, mediated by oxidative stress and an aggressive immune attack on its own cells. In this regard, the use of compounds with high antioxidant activity could have advantages both prophylactically and medically. There is a huge range of natural compounds, including official and traditional medicine, which represent valuable unlimited potential for COVID-19 therapy, the advantage of such compounds in their low toxicity. In this review, we tried to focus on the clinical and pharmacological properties of natural substances, mainly flavonoids, which can become promising drugs for the treatment and prevention of COVID-19. The review includes information on possible virus targets and antiviral drugs. Much attention is paid to the question of inhibition of viral activity. Based on published data, including structural features of various compounds, a prediction is made about the prospects of using these compounds as inhibitors of viral activity, as well as anti-inflammatory drugs for the treatment of COVID-19. An important step in the analysis of compounds was the study of the possibility of their interaction with cellular targets of the virus, as well as the ability to bind to the proteins of the Sars-CoV-2 virus itself. Эпидемия, связанная с новым коронавирусом Sars-CoV-2, поразила практически все страны земного шара, и надежных лечебных средств от этой инфекции пока не существует. Многие лаборатории в мире в настоящее время ведут интенсивные экспериментальные и теоретические исследования с целью поиска эффективных препаратов, специфичных для этого заболевания (COVID-19), но, к сожалению, может потребоваться много времени, прежде чем новые лекарства появятся в клинической практике. Один из самых популярных подходов основан на возможности использования для лечения существующих препаратов, одобренных правительственными медицинскими организациями. Их выбор основан на скрининге, в основе которого лежит использование компьютерных моделей, оценивающих специфическое связывание (минимизация энергии связывания) таких препаратов с молекулами-мишенями, важных для жизненного цикла. Так, ряд известных антивирусных препаратов против ВИЧ, гепатита С, выбранных подобным образом, оказывали противовирусный эффект in vitro, но их клиническая эффективность была невысокой. Следует подчеркнуть, что тяжелая форма клинического проявления заболевания представляет собой острый респираторный дистресс-синдром, опосредованный окислительным стрессом и агрессивной иммунной атакой на собственные клетки. В этой связи применение соединений с высокой антиоксидантной активностью может иметь преимущества как в профилактическом, так и в лечебном плане. Существует огромный спектр природных соединений, включая препараты официальной и традиционной медицины, которые представляют неограниченный потенциал, в том числе для терапии вирусных заболеваний. Основным преимуществом подобных соединений является их низкая токсичность. В данном обзоре мы постарались сделать акцент на клинические и фармакологические свойства природных веществ, преимущественно флавоноидов, которые могут стать перспективными препаратами для лечения и профилактики COVID-19. В обзор включена информация о возможных мишенях вируса и противовирусных препаратах. Большое внимание уделено вопросу ингибирования вирусной активности. На основе литературных данных, в том числе о структурных особенностях различных соединений, сделан прогноз о перспективности использования данных соединений в качестве ингибиторов вирусной активности, а также в качестве противовоспалительных средств для терапии COVID-19. Важным этапом при анализе соединений было изучение возможности их взаимодействия с клеточными мишенями вируса, а также способности связывания с белками самого вируса Sars-CoV-2.