This work aimed to show which treatments showed efficacy against coronavirus disease 2019 (COVID-19); therefore, the results of 37 clinical trials started in 2020 and completed in 2021 are reviewed and discussed here. These were selected from databases, excluding vaccines, computational studies, in silico, in vitro, and those with hyperimmune sera from recovered patients. We found 34 drugs, one vitamin, and one herbal remedy with pharmacological activity against symptomatic COVID-19. They reduced mortality, disease progression, or recovery time. For each treatment, the identifier and type of trial, the severity of the disease, the sponsor, the country where the trial was conducted, and the trial results are presented. The drugs were classified according to their mechanism of action. Several drugs that reduced mortality also reduced inflammation in the most severe cases. These include some that are not considered anti-inflammatory, such as Aviptadil, pyridostigmine bromide, anakinra, imatinib, baricitinib, and bevacizumab, as well as the combination of ivermectin, aspirin, dexamethasone, and enoxaparin. Nigella sativa seeds with honey have also been reported to have therapeutic activity. On the other hand, tofacitinib, novaferon with ritonavir, and lopinavir were also effective, as well as in combination with antiviral therapies such as danoprevir with ritonavir. The natural products colchicine and Vitamin D3 were only effective in patients with mild-to-moderate COVID-19, as was hydroxychloroquine. Drug repositioning has been the main tool in the search for effective therapies by expanding the pharmacological options available to patients.

Important physiological changes are observed in patients with obesity, such as intestinal permeability, gastric emptying, cardiac output, and hepatic and renal function. These differences can determine variations in the pharmacokinetics of different drugs and can generate different concentrations at the site of action, which can lead to sub therapeutic or toxic concentrations. Understanding the physiological and immunological processes that lead to the clinical manifestations of COVID-19 is essential to correlate obesity as a risk factor for increasing the prevalence, severity, and lethality of the disease. Several drugs have been suggested to control COVID- 19 like Lopinavir, Ritonavir, Ribavirin, Sofosbuvir, Remdesivir, Oseltamivir, Oseltamivir phosphate, Oseltamivir carboxylate, Hydroxychloroquine, Chloroquine, Azithromycin, Teicoplanin, Tocilizumab, Anakinra, Methylprednisolone, Prednisolone, Ciclesonide and Ivermectin. Similarly, these differences between healthy people and obese people can be correlated to mechanical factors, such as insufficient doses of the vaccine for high body mass, impairing the absorption and distribution of the vaccine that will be lower than desired or can be linked to the inflammatory state in obese patients, which can influence the humoral immune response. Additionally, different aspects make the obese population more prone to persistent symptoms of the disease (long COVID), which makes understanding these mechanisms fundamental to addressing the implications of the disease. Thus, this review provides an overview of the relationship between COVID-19 and obesity, considering aspects related to pharmacokinetics, immunosuppression, immunization, and possible implications of long COVID in these individuals.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a new coronavirus in the Coronaviridae family. The COVID-19 pandemic, caused by SARS-CoV-2, has undoubtedly been the largest crisis of the twenty-first century, resulting in over 6.8 million deaths and 686 million confirmed cases, creating a global public health issue. Hundreds of notable articles have been published since the onset of this pandemic to justify the cause of viral spread, viable preventive measures, and future therapeutic approaches. As a result, this review was developed to provide a summary of the current anti-COVID-19 drugs, as well as their timeline, molecular mode of action, and efficacy. It also sheds light on potential future treatment options. Several medications, notably hydroxychloroquine and lopinavir/ritonavir, were initially claimed to be effective in the treatment of SARS-CoV-2 but eventually demonstrated inadequate activity, and the Food and Drug Administration (FDA) withdrew hydroxychloroquine. Clinical trials and investigations, on the other hand, have demonstrated the efficacy of remdesivir, convalescent plasma, and monoclonal antibodies, 6-Thioguanine, hepatitis C protease inhibitors, and molnupiravir. Other therapeutics, including inhaled medicines, flavonoids, and aptamers, could pave the way for the creation of novel anti-COVID-19 therapies. As future pandemics are unavoidable, this article urges immediate action and extensive research efforts to develop potent specialized anti-COVID-19 medications.

The SARS-CoV-2 virus, which emerged in December 2019, has infected millions worldwide and caused many deaths. Due to its high mortality rate, several studies assessed the effectiveness of different drugs against COVID-19, mainly in reducing the hospitalization rate among the elderly and compromised patients. Lopinavir-ritonavir combination and remdesivir were among the medications used to treat COVID-19. Due to considerable differences in the effectiveness and clinical outcomes of the two treatments, this study aimed to compare the clinical outcomes between COVID-19 patients treated with antiretrovirals (lopinavir-ritonavir) and remdesivir. A total of 33 patients on lopinavir-ritonavir and 35 on remdesivir were selected for this study. A retrospective comparative analysis was conducted based on demographic characteristics, hospital stay, laboratory parameters of C-reactive protein (CRP) and plasma blood oxygen saturation (SPO2), clinical treatment, and a clinical outcome assessment extracted from hospital archive data. Both treatments improved patient outcomes, yet there was a significant difference between lopinavir-ritonavir and remdesivir groups in platelet count, CRP, SPO2, and monocyte results, with remdesivir showing better clinical outcomes. No significant difference was reported in white blood cells, lymphopenia, and lactate dehydrogenase between the two treatments. It is still necessary to conduct further research to determine how effective the two treatments are in treating severe COVID-19 cases due to the limited number of available studies and the inconsistency in research methods and measurements.

New-onset atrial fibrillation (NOAF) is the most frequently encountered cardiac arrhythmia observed in patients with COVID-19 infection, particularly in Intensive Care Unit (ICU) patients. The purpose of the present review is to delve into the occurrence of NOAF in COVID-19 and thoroughly review recent, pertinent data. However, the causality behind this connection has yet to be thoroughly explored. The proposed mechanisms that could contribute to the development of AF in these patients include myocardial damage resulting from direct virus-induced cardiac injury, potentially leading to perimyocarditis; a cytokine crisis and heightened inflammatory response; hypoxemia due to acute respiratory distress; disturbances in acid-base and electrolyte levels; as well as the frequent use of adrenergic drugs in critically ill patients. Additionally, secondary bacterial sepsis and septic shock have been suggested as primary causes of NOAF in ICU patients. This notion gains strength from the observation of a similar prevalence of NOAF in septic non-COVID ICU patients with ARDS. It is plausible that both myocardial involvement from SARS-CoV-2 and secondary sepsis play pivotal roles in the onset of arrhythmia in ICU patients. Nonetheless, there exists a significant variation in the prevalence of NOAF among studies focused on severe COVID-19 cases with ARDS. This discrepancy could be attributed to the inclusion of mixed populations with varying degrees of illness severity, encompassing not only patients in general wards but also those admitted to the ICU, whether intubated or not. Furthermore, the occurrence of NOAF is linked to increased morbidity and mortality. However, it remains to be determined whether NOAF independently influences outcomes in critically ill COVID-19 ICU patients or if it merely reflects the disease's severity. Lastly, the management of NOAF in these patients has not been extensively studied. Nevertheless, the current guidelines for NOAF in non-COVID ICU patients appear to be effective, while accounting for the specific drugs used in COVID-19 treatment that may prolong the QT interval (although drugs like lopinavir/ritonavir, hydrochlorothiazide, and azithromycin have been discontinued) or induce bradycardia (e.g., remdesivir).

The COVID-19 pandemic has spurred intense research efforts to identify effective treatments for SARS-CoV-2. In silico studies have emerged as a powerful tool in the drug discovery process, particularly in the search for drug candidates that interact with various SARS-CoV-2 receptors. These studies involve the use of computer simulations and computational algorithms to predict the potential interaction of drug candidates with target receptors. The primary receptors targeted by drug candidates include the RNA polymerase, main protease, spike protein, ACE2 receptor, and transmembrane protease serine 2 (TMPRSS2). In silico studies have identified several promising drug candidates, including Remdesivir, Favipiravir, Ribavirin, Ivermectin, Lopinavir/Ritonavir, and Camostat Mesylate, among others. The use of in silico studies offers several advantages, including the ability to screen a large number of drug candidates in a relatively short amount of time, thereby reducing the time and cost involved in traditional drug discovery methods. Additionally, in silico studies allow for the prediction of the binding affinity of the drug candidates to target receptors, providing insight into their potential efficacy. This study is aimed at assessing the useful contributions of the application of computational instruments in the discovery of receptors targeted in SARS-CoV-2. It further highlights some identified advantages and limitations of these studies, thereby revealing some complementary experimental validation to ensure the efficacy and safety of identified drug candidates.

In the field of chemical and medical sciences, topological indices are used to study the chemical, biological, clinical, and therapeutic aspects of pharmaceuticals. The COVID-19 pandemic is largely recognized as the most life-threatening crisis confronting medical advances. Scientists have tested various antiviral drugs and discovered that they help people recover from viral infections like COVID-19. Antiviral medications, such as Arbidol, Chloroquine, Hydroxy-Chloroquine, Lopinavir, Remdesivir, Ritonavir, Thalidomide and Theaflavin, are often used to treat COVID-19. In this paper, we define Diameter Eccentricity Based vertex degree and employ it to introduce a new polynomial called $ D\varepsilon- $ Polynomial. Using the newly introduced polynomial, we derive new topological indices, namely, diameter eccentricity based and hyper diameter eccentricity based indices. In order to check the efficacy of our indices, we derive the $ D\varepsilon- $ polynomials for the eight COVID-19 drugs mentioned above. Using these polynomials, we compute our proposed topological descriptors for the eight COVID-19 drugs. We perform quantitative structure-property relationship (QSPR) analysis by identifying the best fit curvilinear/multilinear regression models based on our topological descriptors for 8 physico- chemical properties of the COVID-19 drugs. We also perform quantitative structure-activity relationship (QSAR) analysis by identifying the best fit multilinear regression model for predicting the $ IC_{50} $ values for the eight COVID-19 drugs. Our findings and models may be useful in the development of new COVID-19 medication.

Since the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), several variants have caused a persistent pandemic. Consequently, it is crucial to develop new potential anti-SARS-CoV-2 drugs with specificity. To minimize potential failures and preserve valuable clinical resources for the development of other useful drugs, researchers must enhance their understanding of the interactions between drugs and SARS-CoV-2. While numerous crystal structures of the SARS-CoV-2 main protease (SCM) and its inhibitors have been reported, they provide only static snapshots and fail to capture the dynamic nature of SCM/inhibitor interactions. Herein, we conducted molecular dynamics simulations for five SCM complexes: ritonavir (SCM/RTV), lopinavir (SCM/LPV), the identified inhibitor N3 (SCM/N3), the approved inhibitor ensitrelvir (SCM/ESV), and the approved drug nirmatrelvir (SCM/NMV). Additionally, we explored the potential for covalent bond formation in the N3 and NMV inhibitors through QM/MM calculations using Umbrella sampling. The results show that the binding site is highly flexible to fit those five different inhibitors and each compound has its unique binding mode at the same binding site. Moreover, the binding affinities of positive and negative inhibitors to SCM exhibit significant differences. By gaining insights into the dynamics, we can potentially elucidate why lopinavir/ritonavir, initially considered promising, failed to effectively treat COVID-19. Furthermore, understanding the mechanistic aspects of N3 and NMV inhibition on SCM not only contributes to rational drug discovery against COVID-19 but also aids future studies on the catalytic mechanisms of main proteases in other novel coronaviruses.Communicated by Ramaswamy H. Sarma.

In the first wave of COVID-19, up to 20% of patients had skin lesions with variable characteristics. There is no clear evidence of the involvement of the SARS-CoV-2 virus in all cases; some of these lesions may be secondary to drug hypersensitivity. To analyze the possible cause of the skin lesions, we performed a complete allergology study on 11 patients. One year after recovery from COVID-19, we performed a lymphocyte transformation test (LTT) and Th1/Th2 cytokine secretion assays for PBMCs. We included five nonallergic patients treated with the same drugs without lesions. Except for one patient who had an immediate reaction to azithromycin, all patients had a positive LTT result for at least one of the drugs tested (azithromycin, clavulanic acid, hydroxychloroquine, lopinavir, and ritonavir). None of the nonallergic patients had a positive LTT result. We found mixed Th1/Th2 cytokine secretion (IL-4, IL-5, IL-13, and IFN-γ) in patients with skin lesions corresponding to mixed drug hypersensitivity type IVa and IVb. In all cases, we identified a candidate drug as the culprit for skin lesions during SARS-CoV-2 infection, although only three patients had a positive drug challenge. Therefore, it would be reasonable to recommend avoiding the drug in question in all cases.

The COVID-19 pandemic has caused havoc in the health sector. Inflammatory cytokines play an important role in the disease condition. Existing evidence has provided certain insights into the repurposing of the drugs. This meta-analysis and systematic review aimed to explore the efficacy of the administration of interferon beta-1b (IFN β-1b) and standard care versus only standard care as the therapeutic agent for managing COVID-19 patients who are severely ill. The search was conducted in the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Scopus, and Google Scholar, which were published during the period January 1, 2020, to February 16, 2023. All the included three studies were independently assessed for eligibility. The modified data extraction form of Cochrane were used. The quality of the three included studies was assessed using the Cochrane risk of bias tool. GradePro software was used to summarize the quality grading of the primary outcome measures. The time taken for clinical improvement was (MD: -3.28 days; 95% CI: -5.65, -0.91; P value = 0.007) when treated with IFN β-1b. The duration of hospital stays (MD: -2.43 days; 95% CI: -4.45, -0.30; P value = 0.03), and need for intensive care unit (ICU) admission (RR: 0.71; 95% CI: 0.52, 0.97; P value = 0.03) was statistically significant. Interferon beta-1b is proven to reduce the duration of hospital stay, and the improved clinical status may become a cornerstone of COVID-19 treatment.

The lack of inclusion of pregnant women in clinical trials evaluating the effectiveness of medicines to treat COVID-19 has made it difficult to establish evidence-based treatment guidelines for pregnant women. Our aim was to provide a review of the evolution and updates of the national guidelines on medicines used in pregnant women with COVID-19 published by the obstetrician and gynecologists' societies in thirteen countries in 2020-2022. Based on the results of the RECOVERY (Randomized Evaluation of COVID-19 Therapy) trial, the national societies successively recommended against prescribing hydroxychloroquine, lopinavir-ritonavir and azithromycin. Guidelines for remdesivir differed completely between countries, from compassionate or conditional use to recommendation against. Nirmatrelvir-ritonavir was authorized in Australia and the UK only in research settings and was no longer recommended in the UK at the end of 2022. After initial reluctance to use corticosteroids, the results of the RECOVERY trial have enabled the recommendation of dexamethasone in case of severe COVID-19 since mid-2020. Some societies recommended prescribing tocilizumab to pregnant patients with hypoxia and systemic inflammation from June 2021. Anti-SARS-CoV-2 monoclonal antibodies were authorized at the end of 2021 with conditional use in some countries, and then no longer recommended in Belgium and the USA at the end of 2022. The gradual convergence of the recommendations, although delayed compared to the general population, highlights the importance of the inclusion of pregnant women in clinical trials and of international collaboration to improve the pharmacological treatment of pregnant women with COVID-19.

COVID-19 caused by the infection of SARS-CoV-2 is still a global concern. WHO reported that from 13 March to 9 April 2023, there were 3 million new cases and approximately 23,000 deaths, mostly occurring in the South-East Asia and Eastern Mediterranean regions, which is predicted due to the new Omicron variant, Arcturus XBB.1.16. Many studies have reported the potency of medicinal plants in enhancing the function of the immune system to combat virus infection. The literature review aimed to describe the efficacy and safety of add-on plant-based drugs for COVID-19 patients. The articles were explored on the PubMed and Cochrane Library databases, and published during 2020-2023. Twenty-two varieties of plants were used as add-on therapy for COVID-19 patients. These plants were Andrographis paniculata, Viola odorata, Withania somnifera, Zingiber officinale, Curcuma longa, Ferula foetida, Centella asiatica, Thymus vulgaris, Citrus sinensis, Eugenia caryophyllus, Boswellia carterii, Elettaria cardamomum, Salvia rosmarinus, Piper nigrum, Alstonia scholaris, Picrorhiza kurroa, Swertia chirata, Caesalpinia crista, Cucurbita maxima, Tinospora cordifolia, Ocimum sanctum, and Allium sativum. The best efficacy of an add-on therapy for COVID-19 patients was found in A. paniculata herbs as a single component in pharmaceutical dosage form or in combination with other plants. The safety of the plant has been confirmed. A. paniculata does not show interaction with remdesivir or favipiravir, however, caution and therapy drug monitoring is needed if A. paniculata is used in combination with lopinavir or ritonavir because a strong noncompetitive inhibition of CYP3A4 may occur.

The infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) started form Wuhan, Chinais a devastating and the incidence rate has increased worldwide. Due to the lack of effective treatment against SARS-CoV-2, various strategies are being tested in China and throughout the world, including drug repurposing. To identify the potent clinical antiretroviral drug candidate against pandemic nCov-19 through computational tools. In this study, we used molecular modelling tool (molecular modelling and molecular dynamics) to identify commercially available drugs that could act on protease proteins of SARS-CoV-2. The result showed that Saquinavir, an antiretroviral medication can be used as a first line agent to treat SARS-CoV-2 infection. Saquinavir showed promising binding to the protease active site compared to other possible antiviral agents such as Nelfinavir and Lopinavir. Structural flexibility is one of the important physical properties that affect protein conformation and function and taking this account we performed molecular dynamics studies. Molecular dynamics studies and free energy calculations suggest that Saquinavir binds better to the COVID-19 protease compared to other known antiretrovirals. Our studies clearly propose repurposing of known protease inhibitors for the treatment of COVID-19 infection. Previously ritonavir and lopinavir were proved an important analogues for SARS and MERS in supressing these viruses. In this study it was found that saquinavir has exhibited good G-score and E-model score compared to other analogues. So saquinavir would be prescribe to cure for nCov-2019 either single drug or maybe in combination with ritonavir.

Periodic pandemics of coronavirus (CoV)-related pneumonia have been a major challenging issue since the outbreak of severe acute respiratory syndrome (SARS) in 2002 and Middle East respiratory syndrome (MERS) in 2012. The ongoing pandemic of CoV disease (COVID-19) poses a substantial threat to public health. As for the treatment options, only limited antiviral agents have been approved hitherto, and clinicians mainly focus on currently available drugs including the conventional antiviral interferons (IFNs). In clinical practice, IFNs, when used either alone or in combination with ribavirin and/or lopinavir/ritonavir, have shown promising outcomes, to some extent, in SARS-CoV or MERS-CoV treatment. Although the efficacy and safety of IFNs in COVID-19 treatment remain unclear, their possible use merits further evaluation. We present a review that summarizes current evidence of IFN treatment for COVID-19 and elaborates on other challenges in terms of the timing of IFN treatment initiation, treatment duration, and IFN type to be used. The review findings suggested that IFN acts by directly inhibiting viral replication and activating immune cell subsets. However, there is a lack of well-designed and controlled clinical trials providing firm evidence for the efficacy or safety of IFN therapy for CoVs. Additionally, critically ill patients with multiple immunosuppression-associated comorbidities may not benefit from IFN therapy, necessitating screening of those patients who would most benefit from IFN treatment.