Aims: Carbon monoxide is a respiratory poison and gaseous signaling molecule. Although CO-releasing molecules (CORMs) deliver CO with temporal and spatial specificity in mammals, and are proven antimicrobial agents, we do not understand the modes of CO toxicity. Our aim was to explore the impact of CO gas per se, without intervention of CORMs, on bacterial physiology and gene expression. Results: We used tightly controlled chemostat conditions and integrated transcriptomic datasets with statistical modeling to reveal the global effects of CO. CO is known to inhibit bacterial respiration, and we found expression of genes encoding energy-transducing pathways to be significantly affected via the global regulators, Fnr, Arc, and PdhR. Aerobically, ArcA—the response regulator—is transiently phosphorylated and pyruvate accumulates, mimicking anaerobiosis. Genes implicated in iron acquisition, and the metabolism of sulfur amino acids and arginine, are all perturbed. The global iron-related changes, confirmed by modulation of activity of the transcription factor Fur, may underlie enhanced siderophore excretion, diminished intracellular iron pools, and the sensitivity of CO-challenged bacteria to metal chelators. Although CO gas (unlike H2S and NO) offers little protection from antibiotics, a ruthenium CORM is a potent adjuvant of antibiotic activity. Innovation: This is the first detailed exploration of global bacterial responses to CO, revealing unexpected targets with implications for employing CORMs therapeutically. Conclusion: This work reveals the complexity of bacterial responses to CO and provides a basis for understanding the impacts of CO from CORMs, heme oxygenase activity, or environmental sources. Antioxid. Redox Signal. 24, 1013–1028.

Aims: Carbon monoxide (CO)-releasing molecules (CORMs) are candidates for animal and antimicrobial therapeutics. We aimed to probe the antimicrobial potential of a novel manganese CORM.Results: [Mn(CO)4S2CNMe(CH2CO2H)], CORM-401, inhibits growth of Escherichia coli and several antibiotic-resistant clinical pathogens. CORM-401 releases CO that binds oxidases in vivo, but is an ineffective respiratory inhibitor. Extensive CORM accumulation (assayed as intracellular manganese) accompanies antimicrobial activity. CORM-401 stimulates respiration, polarizes the cytoplasmic membrane in an uncoupler-like manner, and elicits loss of intracellular potassium and zinc. Transcriptomics and mathematical modeling of transcription factor activities reveal a multifaceted response characterized by elevated expression of genes encoding potassium uptake, efflux pumps, and envelope stress responses. Regulators implicated in stress responses (CpxR), respiration (Arc, Fnr), methionine biosynthesis (MetJ), and iron homeostasis (Fur) are significantly disturbed. Although CORM-401 reduces bacterial growth in combination with cefotaxime and trimethoprim, fractional inhibition studies reveal no interaction.Innovation: We present the most detailed microbiological analysis yet of a CORM that is not a ruthenium carbonyl. We demonstrate CO-independent striking effects on the bacterial membrane and global transcriptomic responses.Conclusions: CORM-401, contrary to our expectations of a CO delivery vehicle, does not inhibit respiration. It accumulates in the cytoplasm, acts like an uncoupler in disrupting cytoplasmic ion balance, and triggers multiple effects, including osmotic stress and futile respiration.Rebound Track: This work was rejected during standard peer review and rescued by rebound peer review (Antioxid Redox Signal 16: 293–296, 2012) with the following serving as open reviewers: Miguel Aon, Giancarlo Biagini, James Imlay, and Nigel Robinson. Antioxid. Redox Signal. 28, 1286–1308.

Introduction: Factors such as comorbidity, age and gender distribution are mostly related to hospitalization, numbers requiring intensive care and case fatality rate. In this review, the fatality rate of coronavirus disease 2019 (COVID-19) in different population health background according to comorbidity, age, gender distribution, and laboratory prognosis for COVID-19. Methodology: The current review was based on the data from copious studies that had homogeneity in relation to the review’s objectives. It included the newest studies from December 2019 to September 2020. The epidemiological reasons for the high morbidity and mortality rates among COVID-19 patients were analyzed in different countries. Results: The highest comorbidity prevalence of COVID-19 was recorded in the United States of America (USA) (93.9%) and Italy (68%). Among population health background factors, comorbidity was the most common cause of COVID-19 fatality in the USA. The mean age of the most COVID-19 fatalities was more than 60 years old. Most of the studies show that 60% of COVID-19 patients were male. The fatality rates for the age group of 80-89 years-old in Korea, China, and Italy were 8.7 %, 14.7 %, and 18.8 % respectively. Lymphocytopenia has been observed in 91% of COVID-19 death cases. C - reactive protein had increased in 40-60% of COVID-19 patients. Conclusions: Many factors contribute to COVID-19 severity and fatality rates. Comorbidity, age, and gender were the main reasons for the Case Fatality Rate. This review recommends to follow preventive measures for overcoming the challenges faced during this emerging pandemic disease.

<b><i>Introduction:</i></b> SARS-CoV-2 is a new type of coronavirus causing a pandemic severe acute respiratory syndrome (SARS-2). Coronaviruses are very diverting genetically and mutate so often periodically. The natural selection of viral mutations may cause host infection selectivity and infectivity. <b><i>Methods:</i></b> This study was aimed to indicate the diversity between human and animal coronaviruses through finding the rate of mutation in each of the spike, nucleocapsid, envelope, and membrane proteins. <b><i>Results:</i></b> The mutation rate is abundant in all 4 structural proteins. The most number of statistically significant amino acid mutations were found in spike receptor-binding domain (RBD) which may be because it is responsible for a corresponding receptor binding in a broad range of hosts and host selectivity to infect. Among 17 previously known amino acids which are important for binding of spike to angiotensin-converting enzyme 2 (ACE2) receptor, all of them are conservative among human coronaviruses, but only 3 of them significantly are mutated in animal coronaviruses. A single amino acid aspartate-454, that causes dissociation of the RBD of the spike and ACE2, and F486 which gives the strength of binding with ACE2 remain intact in all coronaviruses. <b><i>Discussion/Conclusion:</i></b> Observations of this study provided evidence of the genetic diversity and rapid evolution of SARS-CoV-2 as well as other human and animal coronaviruses.

Today, the emerging of the new coronavirus 2019nCoV possesses a global health problem and little is known about its origin. In the current investigation, an evolutionary and molecular epidemiological analysis have provided of this new emerged virus. The phylogenetic trees for animal coronaviruses with the novel coronavirus-2019 have been created using a number of available complete protein sequences of envelope (E), membrane (M), nucleocapsid (N) and spike (S) proteins. The phylogenetic trees analysis illustrated that 2019nCoV in all four proteins are very closely related with coronaviruses isolated from Pangolin (scaly anteater) and Bat-SARS-like-coronavirses because all of them are clustered in the same clade. Whereas, the 2019nCoV is less closely related to coronavirses isolated from Rousettus bat (fruit bat) and MERS coronaviruses isolated from camel because they are gathered in the same clade only in two of the four studied proteins, nucleocapsid (N) and spike (S). In the conclusion, the new 2019nCoV is more likely to be originated from Bat-SARS-like-coronaviruses or/and coronavirus isolated from Pangolin after adaptation and evolution in the human hosts. Because of the number of infected cases to date indicates a very quick human-to-human transmission. Thus, necessitates a very rapid active surveillance using accurate method to find the original host where the 2019nCoV emerged. This will help in further understanding and creating a better approach to control the spread of SARS-CoV-2 outbreak.