Recent insights into SARS-CoV-2 omicron variant.

The SARS-CoV-2 omicron variant (B.1.1.529) was first identified in Botswana and South Africa, and its emergence has been associated with a steep increase in the number of SARS-CoV-2 infections. The omicron variant has subsequently spread very rapidly across the world, resulting in the World Health Organization classification as a variant of concern on 26 November 2021. Since its emergence, great efforts have been made by research groups around the world that have rapidly responded to fill our gaps in knowledge for this novel variant. A growing body of data has demonstrated that the omicron variant shows high transmissibility, robust binding to human angiotensin-converting enzyme 2 receptor, attenuated viral replication, and causes less severe disease in COVID-19 patients. Further, the variant has high environmental stability, high resistance against most therapeutic antibodies, and partial escape neutralisation by antibodies from convalescent patients or vaccinated individuals. With the pandemic ongoing, there is a need for the distillation of literature from primary research into an accessible format for the community. In this review, we summarise the key discoveries related to the SARS-CoV-2 omicron variant, highlighting the gaps in knowledge that guide the field's ongoing and future work.

IN VITRO AND IN VIVO MODELS FOR MONKEYPOX.

The emergence and rapid spread outside of monkeypox virus (MPXV) to nonendemic areas has led to another global health emergency in the midst of the COVID-19 pandemic. The scientific community has sought to rapidly develop in vitro and in vivo models that could be applied in research with MPXV. In vitro models include two-dimensional (2D) cultures of immortalized cell lines or primary cells and three-dimensional (3D) cultures. In vitro models are considered cost-effective and can done in highly controlled conditions, however, they do not always resemble physiological conditions. In this way, several in vivo models are being characterized to meet the growing demand for new studies related to MPXV. In this review, we summarize the main MPXV models that have already been developed and discuss how they can contribute to the advance the understanding of its pathogenesis, replication, and transmission, as well as identifying antivirals to treat infected patients.

Two Years into the COVID-19 Pandemic: Lessons Learned.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and virulent human-infecting coronavirus that emerged in late December 2019 in Wuhan, China, causing a respiratory disease called coronavirus disease 2019 (COVID-19), which has massively impacted global public health and caused widespread disruption to daily life. The crisis caused by COVID-19 has mobilized scientists and public health authorities across the world to rapidly improve our knowledge about this devastating disease, shedding light on its management and control, and spawned the development of new countermeasures. Here we provide an overview of the state of the art of knowledge gained in the last 2 years about the virus and COVID-19, including its origin and natural reservoir hosts, viral etiology, epidemiology, modes of transmission, clinical manifestations, pathophysiology, diagnosis, treatment, prevention, emerging variants, and vaccines, highlighting important differences from previously known highly pathogenic coronaviruses. We also discuss selected key discoveries from each topic and underline the gaps of knowledge for future investigations.

Viral Load in COVID-19 Patients: Implications for Prognosis and Vaccine Efficacy in the Context of Emerging SARS-CoV-2 Variants.

The worldwide spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an unprecedented public health crisis in the 21st century. As the pandemic evolves, the emergence of SARS-CoV-2 has been characterized by the emergence of new variants of concern (VOCs), which resulted in a catastrophic impact on SARS-CoV-2 infection. In light of this, research groups around the world are unraveling key aspects of the associated illness, coronavirus disease 2019 (COVID-19). A cumulative body of data has indicated that the SARS-CoV-2 viral load may be a determinant of the COVID-19 severity. Here we summarize the main characteristics of the emerging variants of SARS-CoV-2, discussing their impact on viral transmissibility, viral load, disease severity, vaccine breakthrough, and lethality among COVID-19 patients. We also provide a rundown of the rapidly expanding scientific evidence from clinical studies and animal models that indicate how viral load could be linked to COVID-19 prognosis and vaccine efficacy among vaccinated individuals, highlighting the differences compared to unvaccinated individuals.

Viral Load in COVID-19 Patients: Implications for Prognosis and Vaccine Efficacy in the Context of Emerging SARS-CoV-2 Variants

The worldwide spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an unprecedented public health crisis in the 21st century. As the pandemic evolves, the emergence of SARS-CoV-2 has been characterized by the emergence of new variants of concern (VOCs), which resulted in a catastrophic impact on SARS-CoV-2 infection. In light of this, research groups around the world are unraveling key aspects of the associated illness, coronavirus disease 2019 (COVID-19). A cumulative body of data has indicated that the SARS-CoV-2 viral load may be a determinant of the COVID-19 severity. Here we summarize the main characteristics of the emerging variants of SARS-CoV-2, discussing their impact on viral transmissibility, viral load, disease severity, vaccine breakthrough, and lethality among COVID-19 patients. We also provide a rundown of the rapidly expanding scientific evidence from clinical studies and animal models that indicate how viral load could be linked to COVID-19 prognosis and vaccine efficacy among vaccinated individuals, highlighting the differences compared to unvaccinated individuals.

Widespread contamination of SARS-CoV-2 on highly touched surfaces in Brazil during the second wave of the COVID-19 pandemic.

Although SARS-CoV-2 surface contamination has been investigated in health care settings, little is known about the SARS-CoV-2 surface contamination in public urban areas, particularly in tropical countries. Here, we investigated the presence of SARS-CoV-2 on high-touch surfaces in a large city in Brazil, one of the most affected countries by the COVID-19 pandemic in the world. A total of 400 surface samples were collected in February 2021 in the City of Recife, Northeastern Brazil. A total of 97 samples (24.2%) tested positive for SARS-CoV-2 by RT-qPCR using the CDC-USA protocol. All the collection sites, except one (18/19, 94.7%) had at least one environmental surface sample contaminated. SARS-CoV-2 positivity was higher in public transport terminals (47/84, 55.9%), followed by health care units (26/84, 30.9%), beach areas (4/21, 19.0%), public parks (14/105, 13.3%), supply centre (2/21, 9.5%), and public markets (4/85, 4.7%). Toilets, ATMs, handrails, playgrounds and outdoor gyms were identified as fomites with the highest rates of SARS-CoV-2 detection. Taken together, our data provide a real-world picture of SARS-CoV-2 dispersion in highly populated tropical areas and identify critical control points that need to be targeted to break SARS-CoV-2 transmission chains.

Computational methods directed towards drug repurposing for COVID-19: advantages and limitations.

Novel coronavirus disease 2019 (COVID-19) has significantly altered the socio-economic status of countries. Although vaccines are now available against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a causative agent for COVID-19, it continues to transmit and newer variants of concern have been consistently emerging world-wide. Computational strategies involving drug repurposing offer a viable opportunity to choose a medication from a rundown of affirmed drugs against distinct diseases including COVID-19. While pandemics impede the healthcare systems, drug repurposing or repositioning represents a hopeful approach in which existing drugs can be remodeled and employed to treat newer diseases. In this review, we summarize the diverse computational approaches attempted for developing drugs through drug repurposing or repositioning against COVID-19 and discuss their advantages and limitations. To this end, we have outlined studies that utilized computational techniques such as molecular docking, molecular dynamic simulation, disease-disease association, drug-drug interaction, integrated biological network, artificial intelligence, machine learning and network medicine to accelerate creation of smart and safe drugs against COVID-19.

Collapse of the public health system and the emergence of new variants during the second wave of the COVID-19 pandemic in Brazil.

The worldwide spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the most severe public health crisis since the 1918 Spanish influenza pandemic. After the introduction of public health interventions aimed at reducing the number of COVID-19 cases, many countries across the world obtained success at containing the fast spread of SARS-CoV-2 during the first wave of the pandemic. However, the SARS-CoV-2 has resurged in many countries causing a even more devastating second wave. Brazil is one the most affected countries and currently is facing one of the worst public health crises in its history. Here, we discuss the unprecedented challenges faced by the Brazilian public health system in the midst of the second wave of the COVID-19 pandemic, particularly regarding the collapse of the Brazilian health system and the emergence of new variants of concern (VOCs). Finally, we suggest some insights using a one health approach that will help the country to face and overcome the current COVID-19 crisis.

In Vitro and In Vivo Models for Studying SARS-CoV-2, the Etiological Agent Responsible for COVID-19 Pandemic.

The emergence and rapid worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has prompted the scientific community to rapidly develop in vitro and in vivo models that could be applied in COVID-19 research. In vitro models include two-dimensional (2D) cultures of immortalized cell lines or primary cells and three-dimensional (3D) cultures derived from lung, alveoli, bronchi, and other organs. Although cell-based systems are economic and allow strict control of experimental variables, they do not always resemble physiological conditions. Thus, several in vivo models are being developed, including different strains of mice, hamsters, ferrets, dogs, cats, and non-human primates. In this review, we summarize the main models of SARS-CoV-2 infection developed so far and discuss their advantages, drawbacks and main uses.

Simultaneous Circulation of DENV, CHIKV, ZIKV and SARS-CoV-2 in Brazil: an Inconvenient Truth.

The emergence of SARS-CoV-2 has prompted the mobilization of a network of public health laboratories to diagnose COVID-19 patients, trace contacts and identify hot-spot areas for active community transmission at the expense of arbovirus diagnosis and control practices. In this article, we discuss the unprecedented challenges faced by the Brazilian public health system in dealing with the incursion of SARS-CoV-2 in the midst of ongoing triple arboviral epidemics caused by dengue, chikungunya, and Zika virus. Finally, we highlight the importance of the introduction of one health approach as an effective inter-disciplinary response and management to mitigate the catastrophic effect caused by these pathogens.

Adaptive, diverse and de-centralized diagnostics are key to the future of outbreak response.

The global spread of SARS-CoV-2 has shaken our health care and economic systems, prompting re-evaluation of long-held views on how best to deliver care. This is especially the case for our global diagnostic strategy. While current laboratory-based centralized RT-qPCR will continue to serve as a gold standard diagnostic into the foreseeable future, the shortcomings of our dependence on this method have been laid bare. It is now clear that a robust diagnostics pandemic response strategy, like any disaster planning, must include adaptive, diverse and de-centralized solutions. Here we look at how the COVID-19 pandemic, and previous outbreaks, have set the stage for a new innovative phase in diagnostics and a re-thinking of pandemic preparedness.

Ivermectin: an award-winning drug with expected antiviral activity against COVID-19.

Ivermectin is an FDA-approved broad-spectrum antiparasitic agent with demonstrated antiviral activity against a number of DNA and RNA viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite this promise, the antiviral activity of ivermectin has not been consistently proven in vivo. While ivermectin's activity against SARS-CoV-2 is currently under investigation in patients, insufficient emphasis has been placed on formulation challenges. Here, we discuss challenges surrounding the use of ivermectin in the context of coronavirus disease-19 (COVID-19) and how novel formulations employing micro- and nanotechnologies may address these concerns.

Epidemiological and clinical characteristics of the first 557 successive patients with COVID-19 in Pernambuco state, Northeast Brazil.

BACKGROUND: South America is the current epicenter of COVID-19 pandemic. Yet, the epidemiological and clinical features of the disease have not been described in Brazil, the third most affected country in the world. METHODS: In this retrospective study, we describe the demographics, epidemiology and clinical features of the first 557 consecutive patients positive for SARS-CoV-2 living in Pernambuco state, Northeast Brazil. RESULTS: The first COVID-19 cases occurred in the high income population. The age of infected patients ranged from 27 days to 97 years with a median of 47 years. The ratio of males to female in the SARS-CoV-2-infected group was 0.83:1. The most common symptom was cough (74.51%), followed by fever (66.79%), dyspnea (56.01%), sore throat (28.19%) and O2 saturation <95% (24.42%). 86.44% of the lethal cases were patients older than 51 years. The median time from illness onset to diagnosis was 4.0 days (range 0-39 days) Severe patients diagnosed after 14 days of symptoms onset had higher viral load than patients with mild disease. CONCLUSIONS: Our study provides important information about COVID-19 in the tropics and will assist physicians and health officials to face the current pandemics as SARS-CoV-2 continues to spread in the human population.

Clinical and Laboratory Diagnosis of SARS-CoV-2, the Virus Causing COVID-19.

In December 2019, a novel beta (ß) coronavirus eventually named SARS-CoV-2 emerged in Wuhan, Hubei province, China, causing an outbreak of severe and even fatal pneumonia in humans. The virus has spread very rapidly to many countries across the world, resulting in the World Health Organization (WHO) to declare a pandemic on March 11, 2020. Clinically, the diagnosis of this unprecedented illness, called coronavirus disease-2019 (COVID-19), becomes difficult because it shares many symptoms with other respiratory pathogens, including influenza and parainfluenza viruses. Therefore, laboratory diagnosis is crucial for the clinical management of patients and the implementation of disease control strategies to contain SARS-CoV-2 at clinical and population level. Here, we summarize the main clinical and imaging findings of COVID-19 patients and discuss the advances, features, advantages, and limitations of different laboratory methods used for SARS-CoV-2 diagnosis.

Insights into SARS-CoV-2, the Coronavirus Underlying COVID-19: Recent Genomic Data and the Development of Reverse Genetics Systems.

The emergence and rapid worldwide spread of a novel pandemic of acute respiratory disease - eventually named coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO) - across the human population has raised great concerns. It prompted a mobilization around the globe to study the underlying pathogen, a close relative of severe acute respiratory syndrome coronavirus (SARS-CoV) called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Numerous genome sequences of SARS-CoV-2 are now available and in-depth analyses are advancing. These will allow detailed characterization of sequence and protein functions, including comparative studies. Care should be taken when inferring function from sequence information alone, and reverse genetics systems can be used to unequivocally identify key features. For example, the molecular markers of virulence, host range and transmissibility of SARS-CoV-2 can be compared to those of related viruses in order to shed light on the biology of this emerging pathogen. Here, we summarize some recent insights from genomic studies and strategies for reverse genetics systems to generate recombinant viruses, which will be useful to investigate viral genome properties and evolution.

Discovery of New Hydroxyethylamine Analogs against 3CLpro Protein Target of SARS-CoV-2: Molecular Docking, Molecular Dynamics Simulation, and Structure-Activity Relationship Studies.

The novel coronavirus, SARS-CoV-2, has caused a recent pandemic called COVID-19 and a severe health threat around the world. In the current situation, the virus is rapidly spreading worldwide, and the discovery of a vaccine and potential therapeutics are critically essential. The crystal structure for the main protease (Mpro) of SARS-CoV-2, 3-chymotrypsin-like cysteine protease (3CLpro), was recently made available and is considerably similar to the previously reported SARS-CoV. Due to its essentiality in viral replication, it represents a potential drug target. Herein, a computer-aided drug design (CADD) approach was implemented for the initial screening of 13 approved antiviral drugs. Molecular docking of 13 antivirals against the 3-chymotrypsin-like cysteine protease (3CLpro) enzyme was accomplished, and indinavir was described as a lead drug with a docking score of -8.824 and a XP Gscore of -9.466 kcal/mol. Indinavir possesses an important pharmacophore, hydroxyethylamine (HEA), and thus, a new library of HEA compounds (>2500) was subjected to virtual screening that led to 25 hits with a docking score more than indinavir. Exclusively, compound 16 with a docking score of -8.955 adhered to drug-like parameters, and the structure-activity relationship (SAR) analysis was demonstrated to highlight the importance of chemical scaffolds therein. Molecular dynamics (MD) simulation analysis performed at 100 ns supported the stability of 16 within the binding pocket. Largely, our results supported that this novel compound 16 binds with domains I and II, and the domain II-III linker of the 3CLpro protein, suggesting its suitability as a strong candidate for therapeutic discovery against COVID-19.