Broad and potent activity against SARS-like viruses by an engineered human monoclonal antibody
C. Garrett RappazzoLongping V. TseChengzi I. KakuDaniel WrappMrunal SakharkarDeli HuangLaura M. DeveauThomas J. YockachonisAndrew S. HerbertMichael B. BattlesCecilia M. O’BrienMichael E. BrownJames C. GeogheganJonathan BelkLinghang PengLinlin YangYixuan J. HouTrevor ScobeyDennis R. BurtonDavid NemazeeJohn M. DyeJames E. VossBronwyn M. GunnJason S. McLellanRalph S. BaricLisa E. GralinskiLaura M. Walker
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Targeting sarbecoviruses As we continue to battle the COVID-19 pandemic, we must confront the possibility of new pathogenic coronaviruses emerging in humans in the future. With this in mind, Rappazzo et al. isolated antibodies from a survivor of the 2003 severe acute respiratory syndrome coronavirus (SARS-CoV), used yeast display libraries to introduce diversity into these antibodies, and then screened for binding to SARS-CoV-2. One of the affinity-matured progeny strongly neutralized SARS-CoV-2, SARS-CoV, and two SARS-related viruses from bats. In addition, this antibody bound to the receptor-binding domains from a panel of sarbecoviruses, suggesting broader activity, and provided protection against SARS-CoV and SARS-CoV-2 in mouse models. Science , this issue p. 823Keywords:
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INTRODUCTION: The pool testing technique optimizes the number of tests performed and reduces the delivery time of results, which is an interesting strategy for the health crisis caused by the COVID-19 pandemic. This integrative review investigated studies in which pool testing was carried out for epidemiological or screening purposes to analyze its clinical or cost effectiveness and assessed the applicability of this method in high-, middle-, and low-income countries. METHODS: This integrative review used primary studies published in the MEDLINE, EMBASE, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), and Cochrane Library databases. RESULTS: A total of 435 studies were identified: 35.3% were carried out in Asia, 29.4% in Europe, 29.4% in North America, and 5.9% in Oceania. CONCLUSIONS: This review suggests that pool testing in the general population may be a useful surveillance strategy to detect new variants of SARS-CoV-2 and to evaluate the period of immunogenicity and global immunity from vaccines.
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There have been millions of cases of Coronavirus, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with high infectious properties during the year 2019. To counter the situation, certain medications were prescribed by health experts, such as Remdesivir, Dexamethasone, Azithromycin and Hydroxychloroquine, following the World Health Organization (WHO) guidelines. While vaccines have since been administered to alleviate symptoms, alternative treatments like Ayurvedic remedies are being explored. This study specifically delves into in-silico analysis using Autodock 4.2.6 software to assess selected phytomarkers against the 6LU7 main protease protein. The chemical structures of these drugs were analyzed using SWISSADME software to evaluate their drug-likeness properties. Molecular docking was conducted using Autodock tools 1.5.6, and receptor-ligand interactions were visualized using PyMol 2.3. Discovery Studio Visualizer 2020 generated a two-dimensional map illustrating bond interactions and distances between drugs and receptors. The mean binding energies of the compounds, including Nobiletin, Tangeretin, Sideroxylonal C, Coriandron, Epicatechin, Epigallocatechin gallate, Luteolin, Ombuin, Tamarixetin, 6-deacetylnimbin, Nimbolide, and Tricin were -5.66, -6.00, -6.46, -6.40, -6.91, -6.51, -6.34, -6.46, -6.99, -6.82, -6.51, -7.85, and -6.35 kcal/mol. Notably, several bioactive markers, including Nobiletin, Tangeretin, Epicatechin, Epigallocatechin gallate (EGCG), Ombuin, Tamarixetin, and Nimbolide, exhibited similar binding sites to synthetic drugs like Remdesivir, such as PHE140, CYS145, GLU166, and GLN189. The investigation also addresses Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) modelling, binding energy scores, and binding affinity, emphasizing the importance of vaccination as a crucial measure to curb the spread of infection.
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The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still threatening global health.According to the latest data, the number of diagnosed cases has exceeded 100 million.Comfortingly, experiences have been accumulated in preventing and treating COVID-19 through virological, immunological, epidemiological, and clinical investigations of this disease. 1Besides, the continuous advancement of different vaccines brings the dawn to defeat the epidemic. 2However, the emergence of fast-spreading SARS-CoV-2 mutant strains (B.1.1.7,B.1.351,and B.1.1.28.1) was reported at the end of 2020, causing concern to prevention and treatment of COVID-19.It is speculated that the emergence of the SARS-CoV-2 variants may portend a new phase of the pandemic. 3 EMERGENCE AND GLOBAL SPREAD OF SARS-COV-2 VARIANTSThe SARS-CoV-2 is a kind of RNA virus.Due to the lack of a mismatch repair mechanism, the virus replication process is accompanied by a high mutation rate. 4Hence, the mutations of the coronavirus are commonsensical and predictable.Mutations could make the virus more contagious and difficult to be eliminated.For instance, the D614G (the amino acid at position 614 was mutated from aspartic acid to glycine) variant, identified by Korber et al. 5 , is more transmissible and had been dominated worldwide. 6,7At present, three novel variants, B.1.1.7,B.1.351,and B.1.1.28.1, have rapidly spread worldwide, causing concerns about the prevention and treatment of COVID-19.The B.1.1.7 (known as 20I/501Y.V1 or VOC 202012/01) was firstly isolated and identified in Kent and Greater London, the United Kingdom.Within several weeks, the new strain swept across the UK and was detected in numerous countries.The variant emerged with multiple mutation sites, including six synonymous mutations, 13 non-synonymous mutations, and four deletion mutations (Fig. 1a). 8he mutant strain B.1.351,also known as 20H/501Y.V2, was first reported by the Centre for the AIDS Programme of Research in South Africa on December 18, 2020.The lineage was early detected in the coastal areas of the Eastern Cape of South African and predominated the Eastern Cape and Western Cape within a few weeks. 9,10The new lineage emerged with 21 mutations, 10 among which nine mutations were identified in the spike protein region (Fig. 1a).The lineage B.1.1.28.1 (also known as P.1) was first reported by the National Institute of Infectious Diseases in Japan on January 6, 2021, in four travelers from Brazil.The P.1 variant outbreak had mainly found in Manaus, 11,12 which had been experienced widespread infections in May, 2020.This strain carries 21 mutations, including one insertion, one deletion, four synonymous mutations, and 15 non-synonymous mutations (Fig. 1a).Compared with 501Y.V1 and 501Y.V2, the P.1 variant emerged with more changes (10 mutations) in spike protein. 12A recent study pointed out the P.1 variant caused the second outbreak in Manaus, 11 raising the concern that immune evasion is triggered by new lineages.Furthermore, several new SARS-CoV-2 variants have been isolated in many states of the US recently.The team at Southern Illinois University had been identified a new variant in the United States.The variant named 20C-US can be traced in May of 2020, and the main mutation occurs in Q677 and Q173 of the spike protein. 13The Q677H mutation near the protease cleavage site may affect the stability of the spike protein.The detailed biological effects and virus characteristics of 20C-US remain to be characterized.Researchers have reported a novel variant, called CAL.20C, appearing in Southern California.The strain was derived from cluster 20C and had five unique mutations (one in ORF1a: I4205V, one in ORF1b: D1183Y, three in spike protein: S13I, W152C, and L452R). 14The novel strain spans the B.1.427and B.1.429lineages, accounted for more than 50 percent of Los Angeles sequence samples.Scholars speculate that the CAL.20C may be one reason for the recent surge in California cases.The new SARS-CoV-2 variant, known as B.1.526,has been identified by the Columbia University.This newly identified strain emerges with multiple mutations in the spike protein, including L5F, T95I, D253G, E484K, D614G, and A701V. 15,16The new strain is spreading rapidly, and the number of patients infected with the variant has accounted for more than 20% of New York cases.Besides, the variant named B.1.525has also spread in New York City.The B.1.525lineage was firstly identified in the UK on December 15, 2020 and became the dominant lineage in Nigeria.It has four mutations (Q52R, E484K, Q677, and F888L) in the spike protein region and a deletion mutation (ΔH69/ΔV70) similar to B.1.1.7 lineage.According to the latest World Health Organization (WHO) data, we summarized multiple variants in Table 1.
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Victoria's second wave of SARS-CoV-2 infections saw a number of reports of deaths of SARS-CoV-2 positive persons made to the coroner. Whilst COVID-19 deaths are natural and do not routinely fall under the coroner's jurisdiction, these cases were brought to the coroner's attention due to deaths being unexpected and unexplained and subsequently being diagnosed as COVID-19 post-mortem, concerns around care in those dying with a known diagnosis of COVID-19, or co-incidental SARS-CoV-2 infection with a cause of death unrelated to viral infection. This had a significant impact on workloads at VIFM, ranging from changes in admission procedures, extensive viral testing, and contributions to contact tracing. Aspects of the management of these cases will be discussed, along with the pathological aspects of some of these presentations.
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В статье предлагается комбинированная терапия для SARS-CoV-2, включающая в себя применение настоя из лекарственных растений, богатых натуральными алкалоидами. Известно, что алкалоиды имеют противовирусное воздействие, основанное на ингибиции репликации вируса путем блокирования активности вирусной ДНК-полимеразы. Этот подход мог бы способствовать поиску терапевтического решения проблемы COVID-19.
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A severe form of respiratory disease – COVID-19, caused by SARS-CoV-2 infection, has evolved into a pandemic resulting in significant morbidity and mortality. The unabated spread of the disease is due to lack of vaccine and effective therapeutic agents against this novel virus. Hence, the situation demands an immediate need to explore all the plausible therapeutic and prophylactic strategies that can be made available to stem the spread of the disease. Towards this effort, the current review outlines the key aspects of the pathobiology associated with the morbidity and mortality in COVID-19 patients, which includes a viral response phase and an exaggerated host response phase. The review also summarizes therapeutic agents that are currently being explored along with those with potential for consideration. The broad groups of therapeutic agents discussed include those that: (i) block viral entry to host cells, (ii) block viral replication and survival in host cells, and (iii) dampen exaggerated host immune response. The various kinds of pharmaceutical prophylactic options that may be followed to prevent COVID-19 have also been discussed.
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