Transmission, Prevention and Therapeutic Strategies for COVID-19: Updates and Challenges

Background: Almost the whole world is observing a pandemic like never before in the last century, affecting the human lifestyle and economies known as coronavirus disease-2019 (COVID-19). A new severe acute respiratory syndrome that has emerged in China in late 2019 and spread in more than 210 countries makes a global health care emergency. Objective(s): Considering the epidemiological features of COVID-19, it is crucial to prevent the spread of such a highly infectious disease through effective control methods such as early detec-tion, isolation, and treatment strategies. Conclusion(s): This review highlights the SARS-CoV-2 transmission routes among communities and control measures, improving the quarantine and isolation of infected individuals. The "gold stan-dard" molecular and other rapid diagnostic tests used to detect SARS-CoV-2 with their benefits and limitations have been reported. Several repurposed drugs, including antivirals trailed for COVID-19 patients, and supportive treatments, such as general, cellular, and immune therapies with the role of vitamins in the safe deployment for COVID-19 patients, have been discussed. Fi-nally, the review also encompasses an overview and update about the recent development of COVID-19 vaccines and ongoing clinical studies, providing further research advances.Copyright © 2021 Bentham Science Publishers.

New Aspect of Candida spp. Infections

Candidiasis is an opportunistic fungal infection resulting from an imbalance between the host immune system and crucial virulence factors of Candida species. The Candida spp., are one of the major constituents of the human mycobiome as well as the main cause of invasive fungal infections, particularly in immunocompromised patients. They affect the cases who consume a wide-spectrum antibiotic/steroid and those who have prolonged ICU stays and central venous catheters, transplant patients, chemotherapy/ radiotherapy, patients under invasive or noninvasive ventilation, and diabetic individuals with high-rate mortality. In recent decades, Candida species are considered the fourth cause of bloodstream infections;however, the epidemiology of candidemia has been linked to different geographical areas. On the other hand, the emergence of multidrug-resistant Candida spp. named Candia auris, as a global challenge in different countries over recent years in the world, leads to lethal as well as invasive infections with a high rate of spread among patients. At the beginning of the novel coronavirus disease 2019 (COVID-19) pandemic with causative agent of severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), invasive yeast infections (IYFs), especially Candidiasis, are dramatically increasing in those individuals as the major groups under immunosuppressed condition. Although echinocandins and azoles are the most common antifungals used for the treatment of IYFs, the increased therapeutic failures exerted by multidrug-resistant Candida spp. such as C. auris and C. glabrata, calling for the discovery of novel antifungal agents with therapeutic approaches seems necessary. Here, we attempt to focus on the acquisition of knowledge associated with pathogenicity of Candida spp., particularly the indispensable role of virulence factors (germination, adherence, biofilm formation, phospholipase and proteinase production), genes that contribute to drug resistance and the related mechanisms, new therapeutic strategies for the treatment of Candidiasis includes combination therapies, application of biomaterials for drug delivery, antibodies, and vaccination, photodynamic therapy, probiotics, and new antifungal products to overcome Candida infections. © 2023 Nova Science Publishers, Inc.

2020 update on human coronaviruses: One health, one world.

Since human coronavirus (HCoVs) was first described in the 1960s, seven strains of respiratory human coronaviruses have emerged and caused human infections. After the emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), a pneumonia outbreak of coronavirus disease 2019 (COVID-19) caused by a novel coronavirus (SARS-CoV-2) has represented a pandemic threat to global public health in the 21st century. Without effectively prophylactic and therapeutic strategies including vaccines and antiviral drugs, these three coronaviruses have caused severe respiratory syndrome and high case-fatality rates around the world. In this review, we detail the emergence event, origin and reservoirs of all HCoVs, compare the differences with regard to structure and receptor usage, and summarize therapeutic strategies for COVID-19 that cause severe pneumonia and global pandemic.

Alternatives Therapeutic Approaches to Conventional Antibiotics: Advantages, Limitations and Potential Application in Medicine.

Resistance to antimicrobials and particularly multidrug resistance is one of the greatest challenges in the health system nowadays. The continual increase in the rates of antimicrobial resistance worldwide boosted by the ongoing COVID-19 pandemic poses a major public health threat. Different approaches have been employed to minimize the effect of resistance and control this threat, but the question still lingers as to their safety and efficiency. In this context, new anti-infectious approaches against multidrug resistance are being examined. Use of new antibiotics and their combination with new ß-lactamase inhibitors, phage therapy, antimicrobial peptides, nanoparticles, and antisense antimicrobial therapeutics are considered as one such promising approach for overcoming bacterial resistance. In this review, we provide insights into these emerging alternative therapies that are currently being evaluated and which may be developed in the future to break the progression of antimicrobial resistance. We focus on their advantages and limitations and potential application in medicine. We further highlight the importance of the combination therapy approach, wherein two or more therapies are used in combination in order to more effectively combat infectious disease and increasing access to quality healthcare. These advances could give an alternate solution to overcome antimicrobial drug resistance. We eventually hope to provide useful information for clinicians who are seeking solutions to the problems caused by antimicrobial resistance.

IL-33 and the Cytokine Storm in COVID-19: From a Potential Immunological Relationship towards Precision Medicine.

Coronavirus SARS-CoV-2 has represented, and still represents, a real challenge from a clinical, diagnostic and therapeutic point of view. During acute infection, the increased levels of pro-inflammatory cytokines, which are involved in the pathology of disease and the development of SARS-CoV-2-induced acute respiratory disease syndrome, the life-threatening form of this infection, are correlated with patient survival and disease severity. IL-33, a key cytokine involved in both innate and adaptive immune responses in mucosal organs, can increase airway inflammation, mucus secretion and Th2 cytokine synthesis in the lungs, following respiratory infections. Similar to cases of exposure to known respiratory virus infections, exposure to SARS-CoV-2 induces the expression of IL-33, correlating with T-cell activation and lung disease severity. In this work, we analyse current evidence regarding the immunological role of IL-33 in patients affected by COVID-19, to evaluate not only the clinical impact correlated to its production but also to identify possible future immunological therapies that can block the most expressed inflammatory molecules, preventing worsening of the disease and saving patient lives.

A Review of Potential Therapeutic Strategies for COVID-19.

Coronavirus disease 2019 is a rather heterogeneous disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The ongoing pandemic is a global threat with increasing death tolls worldwide. SARS-CoV-2 belongs to lineage B ß-CoV, a subgroup of Sarbecovirus. These enveloped, large, positive-sense single-stranded RNA viruses are easily spread among individuals, mainly via the respiratory system and droplets. Although the disease has been gradually controlled in many countries, once social restrictions are relaxed the virus may rebound, leading to a more severe and uncontrollable situation again, as occurred in Shanghai, China, in 2022. The current global health threat calls for the urgent development of effective therapeutic options for the treatment and prevention of SARS-CoV-2 infection. This systematic overview of possible SARS-CoV-2 therapeutic strategies from 2019 to 2022 indicates three potential targets: virus entry, virus replication, and the immune system. The information provided in this review will aid the development of more potent and specific antiviral compounds.

COVID-19 outbreak

The outbreak of the pandemic, COVID-19, triggered by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) throughout the world took a large number of lives till today and even counting. We have made an effort in this critical hour to compile and contemplate the literature reported till July 13, 2020 about the structure and morphology, epidemiology, transmission, replication cycle, and potential therapeutic strategies to tackle this pandemic. We have also highlighted some unexplored targets and potential gateways for the researchers in the field which may help to unravel some breakthrough therapy against this infection. Additionally, we have focused on the different approaches for vaccine development which could be used by researchers to develop a vaccine strong enough to eradicate this viral infection and to improve the current healthcare of the infected patients. © 2022 Elsevier Inc. All rights reserved.

Pulmonary resident memory T cells in respiratory virus infection and their inspiration on therapeutic strategies.

The immune system generates memory cells on infection with a virus for the first time. These memory cells play an essential role in protection against reinfection. Tissue-resident memory T (TRM) cells can be generated in situ once attacked by pathogens. TRM cells dominate the defense mechanism during early stages of reinfection and have gradually become one of the most popular focuses in recent years. Here, we mainly reviewed the development and regulation of various TRM cell signaling pathways in the respiratory tract. Moreover, we explored the protective roles of TRM cells in immune response against various respiratory viruses, such as Respiratory Syncytial Virus (RSV) and influenza. The complex roles of TRM cells against SARS-CoV-2 infection are also discussed. Current evidence supports the therapeutic strategies targeting TRM cells, providing more possibilities for treatment. Rational utilization of TRM cells for therapeutics is vital for defense against respiratory viruses.

Target-Specific Drug Discovery of Natural Products against SARS-CoV-2 Life Cycle and Cytokine Storm in COVID-19.

Coronavirus disease 2019 (COVID-19) is currently a worldwide pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, there are no drugs that can specifically combat SARS-CoV-2. Besides, multiple SARS-CoV-2 variants are circulating globally. These variants may lead to immune escape or drug resistance. Natural products may be appropriate for this need due to their cost efficiency, fewer side effects, and antiviral activities. Considering these circumstances, there is a need to develop or discover more compounds that have potential to target SARS-CoV-2. Therefore, we searched for articles on natural products describing anti-SARS-CoV-2 activities by targeting the SARS-CoV-2 life cycle and the cytokine storm in COVID-19 from academic databases. We reviewed anti-SARS-CoV-2 activities of natural products, especially those that target the SARS-CoV-2 life cycle (angiotensin-converting enzyme 2, transmembrane serine protease 2, cathepsin L, 3CL protease, PL protease, RNA-dependent RNA polymerase, and helicase) and cytokine storm in COVID-19. This review may provide a repurposed approach for the discovery of specific medications using natural products to treat COVID-19 through targeting the SARS-CoV-2 life cycle and the cytokine storm in COVID-19.

An immunologist's guide to immunosenescence and its treatment.

INTRODUCTION: Aging causes several changes in the immune system, although immune aging is strongly influenced by individual immunological history, as well as genetic and environmental factors leading to inter-individual variability. AREAS COVERED: We focused on the biological and clinical meaning of immunosenescence. SARS-CoV-2 and Yellow Fever vaccine have demonstrated the clinical relevance of immunosenescence, while inconsistent results, obtained from longitudinal studies aimed at looking for immune risk phenotypes, have revealed that immunosenescence is highly context-dependent. Large projects allowed the delineation of the drivers of immune system variance, including genetic and environmental factors, sex, smoking, and co-habitation. Therefore, it is difficult to identify the interventions that can be envisaged to maintain or improve immune function in older people. That suggests that drug treatment of immunosenescence should require personalized intervention. Regarding this, we discussed the role of changes in lifestyle as a potential therapeutic approach. EXPERT OPINION: Our review points out that age is only part of the problem of immunosenescence. Everyone ages differently because is unique in genetics and experience of life and this applies even more to the immune system (immunobiography). Finally, the review shows how appreciable results in the modification of immunosenescence biomarkers can be achieved with lifestyle modification.

Molecular mechanisms involved in pathogenicity of SARS-CoV-2: Immune evasion and implications for therapeutic strategies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the outbreak of unusual viral pneumonia that emerged in late 2019 in the city of Wuhan, China. Since then, because of its high transmission and pathogenic potential it spread almost all over the world causing the pandemic, as an extraordinary threat to the world public health. Rapid activation of a well-orchestrated and functional immune system with its both arms innate and adaptive immune response is pivotal to eradication of the disease caused by this coronavirus (COVID-19). Therefore, in this review are summarized the most recent data on complex molecular mechanisms involved in the innate and adaptive immune response to combat COVID-19. In addition to widely used vaccines against SARS-CoV-2, because of the induction of short-lived immunity and appearance of variants of concern (VOCs), there will be also discussed newly developed strategies to target different viral proteins, which are not prone to frequent mutations. Obviously, SARS-CoV-2 cannot evade the effect of these novel drugs and therefore they show a great promise as an antiviral therapy not only in COVID-19 but also in future viral outbreaks.

Pathogenesis of the SARS Coronavirus-2 and Potential Therapeutic Strategies

The recent outbreak of severe acute respiratory syndrome (SARS) belongs to a broad family of viruses known as Coronaviridae. SARS-CoV-2 is an emerging global pandemic with a relatively low mortality rate. The virus has been mutated in a unique manner thus prolonging its search for its vaccine and drug therapy. SARS-CoV-2 is an enveloped virus consisting of many spike (S) proteins, which mediates its fusion to the membrane of the host cell. Its ‘crown-like’ appearance under an electron microscope has led to its name. The clinical symptoms that patients experience would be due to their central immune response to the infection. Pro-inflammatory cytokines play an essential role in cell growth and regulation of the immune system. However, its abundance could contribute to pathological conditions which can cause further injury and possible death. This brief review discusses the pathogenesis of the SARS-CoV-2 along with receptors that can be potentially targeted by therapeutic strategies, inhibiting the membrane fusion, genome replication and immune response. © 2022: Author(s).

The constellation of cholesterol-dependent processes associated with SARS-CoV-2 infection.

The role of cholesterol in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other coronavirus-host cell interactions is currently being discussed in the context of two main scenarios: i) the presence of the neutral lipid in cholesterol-rich lipid domains involved in different steps of the viral infection and ii) the alteration of metabolic pathways by the virus over the course of infection. Cholesterol-enriched lipid domains have been reported to occur in the lipid envelope membrane of the virus, in the host-cell plasma membrane, as well as in endosomal and other intracellular membrane cellular compartments. These membrane subdomains, whose chemical and physical properties distinguish them from the bulk lipid bilayer, have been purported to participate in diverse phenomena, from virus-host cell fusion to intracellular trafficking and exit of the virions from the infected cell. SARS-CoV-2 recruits many key proteins that participate under physiological conditions in cholesterol and lipid metabolism in general. This review analyses the status of cholesterol and lipidome proteins in SARS-CoV-2 infection and the new horizons they open for therapeutic intervention.

COVID-19 and its effects on neurological expressions

Coronavirus disease-19 (COVID-19) is the preeminent global pandemic among infectious diseases in the 21st century. This disease has resulted from the known type of severe acute respiratory syndrome coronavirus 2. There is a widespread among researchers that the zoonotic originated species (i.e., bats and pangolins) are the vital hosts for spreading COVID-19 infection. The potential of COVID-19‘s devastative transmission behavior into the central nervous system (CNS) has created a massive threat among people of various ages. Currently, three criteria are assumed to be the possible strategies for disseminating COVID-19. The morphological characteristics of spike (S) protein are the initial triggering points for the virus transmission. Next, the brain or related CNS organs are the supportive routes for entering the virus. The third criterion may be neuroinflammatory responses, which may speed up viral replication and trigger other serious complications. Hence, in the present chapter we reviewed these criteria for studying the neurological effects that are adverse by COVID-19. Moreover, this chapter deals with the possible limitations and future perspectives for therapeutic strategies and treatment options against COVID-19. © 2021 Elsevier Inc. All rights reserved.

Advances in the development of therapeutic strategies against COVID-19 and perspectives in the drug design for emerging SARS-CoV-2 variants.

Since Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was identified in late 2019, the coronavirus disease 2019 (COVID-19) pandemic has challenged public health around the world. Currently, there is an urgent need to explore antiviral therapeutic targets and effective clinical drugs. In this study, we systematically summarized two main therapeutic strategies against COVID-19, namely drugs targeting the SARS-CoV-2 life cycle and SARS-CoV-2-induced inflammation in host cells. The development of above two strategies is implemented by repurposing drugs and exploring potential targets. A comprehensive summary of promising drugs, especially cytokine inhibitors, and traditional Chinese medicine (TCM), provides recommendations for clinicians as evidence-based medicine in the actual clinical COVID-19 treatment. Considering the emerging SARS-CoV-2 variants greatly impact the effectiveness of drugs and vaccines, we reviewed the appearance and details of SARS-CoV-2 variants for further perspectives in drug design, which brings updating clues to develop therapeutical agents against the variants. Based on this, the development of broadly antiviral drugs, combined with immunomodulatory, or holistic therapy in the host, is prior to being considered for therapeutic interventions on mutant strains of SARS-CoV-2. Therefore, it is highly acclaimed the requirements of the concerted efforts from multi-disciplinary basic studies and clinical trials, which improves the accurate treatment of COVID-19 and optimizes the contingency measures to emerging SARS-CoV-2 variants.

Therapeutic Strategies for COVID-19 Patients: An Update.

The novel coronavirus SARS-coV-2, which emerged in Wuhan in November 2019, has increasingly spread, causing a global pandemic that infected more than 444 million people, resulting in severe social and economic ramifications, and claimed more than 6,010,000 lives by March 5, 2022. The pandemic attracted global attention with consequential multiple economic, social, and clinical studies. Among causes of poor clinical outcomes of the disease are therapeutic challenges, leading to spirals of studies in search of better therapeutic alternatives. Despite the worsening circumstances of the pandemic, no drug has yet shown remarkable efficacy in the clinical management of COVID-19 patients in large-scale trials. Many potential therapeutic strategies, including the use of nucleotide analogs, chloroquine phosphate, arbidol, protease inhibitors (lopinavir/ritonavir), plasma, monoclonal antibodies, plastic antibodies based on molecularly imprinted polymers (MIPs), traditional Chinese medicine (TCM), nanomaterials, vaccine, and mesenchymal stem cells (MSCs), have emerged with various degrees of successes. Remdesivir and dexamethasone have now been licensed based on the results of randomized controlled trials. Baricitinib, the Janus kinase (JAK) 1/2 inhibitor, is also an attractive candidate due to its properties as a potent anti-inflammatory agent and its hypothesized offtarget antiviral effects against SARS-CoV-2. Besides, human plasma from recovered COVID-19 patients is theoretically expected to be safe and effective for both therapy and post-exposure prophylaxis. In light of the literature, the correlation between the reduction of C5aR1/C5aR2 and the IL6-IL6R axis, using the available anti-IL6R mAb would be crucial. Moreover, MSCs are a potential therapeutic choice for patients with COVID-19 pneumonia. The coronavirus spike (S) protein that mediates the process of the infection via binding of host cells to the virus receptor is an essential focus for vaccine development. Importantly, with the number of patients increasing daily, there is an urgent need for effective therapeutic intervention. In this review, we expatiated on several strategies deployed for the treatment of COVID-19 infection.

Healthy Immunity on Preventive Medicine for Combating COVID-19.

Immunomodulation is influenced by the consumption of nutrients, and healthy immunity is pivotal to defending an individual from a variety of pathogens. The immune system is a network of intricately regulated biological processes that is comprised of many organs, cellular structures, and signaling molecules. A balanced diet, rich in vitamins, minerals, and antioxidants, is key to a strengthened immune system and, thus, crucial to proper functioning of various physiological activities. Conversely, deficiencies of these micronutrients, involving impaired immunity, are linked to numerous health complications, along with a host of pathologies. Coronavirus disease 2019 (COVID-19) is a dangerous infectious disease caused by a ß-form of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its genomic variants, which enter host cells upon binding to the angiotensin converting enzyme 2 receptors, and is associated with substantial morbidities and mortalities globally. Patients afflicted with COVID-19 display asymptomatic to severe symptoms, occurrences of which are multifactorial and include diverse immune responses, sex and gender differences, aging, and underlying medical conditions. Geriatric populations, especially men in comparison to women, regardless of their states, are most vulnerable to severe COVID-19-associated infections and complications, with fatal outcomes. Advances in genomic and proteomic technologies help one understand molecular events, including host-pathogen interactions and pathogenesis of COVID-19 and, subsequently, have developed a variety of preventive measures urgently, ranging from mask wearing to vaccination to medication. Despite these approaches, no unique strategy is available today that can effectively prevent and/or treat this hostile disease. As a consequence, the maintenance of a boosted immune system could be considered a high priority of preventive medicine for combating COVID-19. Herein, we discuss the current level of understanding underlining the contribution of healthy immunity and its relevance to COVID-19 molecular pathogenesis, and potential therapeutic strategies, in the management of this devastating disease.

Can Panax ginseng help control cytokine storm in COVID-19?

Coronavirus disease 2019 (COVID-19) is currently a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 are directly associated with hyper-activation of innate immune response that excessively produce pro-inflammatory cytokines and induce cytokine storm, leading to multi-organ-failure and significant morbidity/mortality. Currently, several antiviral drugs such as Paxlovid (nirmatrelvir and ritonavir) and molnupiravir are authorized to treat mild to moderate COVID-19, however, there are still no drugs that can specifically fight against challenges of SARS-CoV-2 variants. Panax ginseng, a medicinal plant widely used for treating various conditions, might be appropriate for this need due to its anti-inflammatory/cytokine/viral activities, fewer side effects, and cost efficiency. To review Panax ginseng and its pharmacologically active-ingredients as potential phytopharmaceuticals for treating cytokine storm of COVID-19, articles that reporting its positive effects on the cytokine production were searched from academic databases. Experimental/clinical evidences for the effectiveness of Panax ginseng and its active-ingredients in preventing or mitigating cytokine storm, especially for the cascade of cytokine storm, suggest that they might be beneficial as an adjunct treatment for cytokine storm of COVID-19. This review may provide a new approach to discover specific medications using Panax ginseng to control cytokine storm of COVID-19.

Elements and COVID-19: A Comprehensive Overview of Studies on Their Blood/Urinary Levels and Supplementation with an Update on Clinical Trials.

The current report provides a brief overview of the clinical features, hematological/biochemical abnormalities, biomarkers, and AI-related strategies in COVID-19; presents in a nutshell the pharmacological and non-pharmacological therapeutic options; and concisely summarizes the most important aspects related to sociodemographic and behavioral factors as well as comorbidities having an impact on this disease. It also gives a brief outline of the effect of selected elements on immune response and collects data on the levels of micro-/macro-elements and toxic metals in the blood/urine of SARS-CoV-2 infected patients and on supplementation with minerals in COVID-19 subjects. Moreover, this review provides an overview of clinical trials based on the use of minerals alone or in combination with other agents that can provide effective responses toward SARS-CoV-2 infection. The knowledge compiled in this report lays the groundwork for new therapeutic treatments and further research on biomarkers that should be as informative as possible about the patient's condition and can provide more reliable information on COVID-19 course and prognosis. The collected results point to the need for clarification of the importance of mineral supplementation in COVID-19 and the relationships of the levels of some minerals with clinical improvement.

JAK-STAT Pathway: A Novel Target to Tackle Viral Infections.

Modulation of the antiviral innate immune response has been proposed as a putative cellular target for the development of novel pan-viral therapeutic strategies. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is especially relevant due to its essential role in the regulation of local and systemic inflammation in response to viral infections, being, therefore, a putative therapeutic target. Here, we review the extraordinary diversity of strategies that viruses have evolved to interfere with JAK-STAT signaling, stressing the relevance of this pathway as a putative antiviral target. Moreover, due to the recent remarkable progress on the development of novel JAK inhibitors (JAKi), the current knowledge on its efficacy against distinct viral infections is also discussed. JAKi have a proven efficacy against a broad spectrum of disorders and exhibit safety profiles comparable to biologics, therefore representing good candidates for drug repurposing strategies, including viral infections.