Emergence of SARS and COVID-19 and preparedness for the next emerging disease X

Severe acute respiratory syndrome(SARS)and Coronavirus disease 2019(COVID-19)are two human Coronavirus diseases emerging in this century,posing tremendous threats to public health and causing great loss to lives and economy.In this review,we retrospect the studies tracing the molecular evolution of SARS-CoV,and we sort out current research findings about the potential ancestor of SARS-CoV-2.Updated knowledge about SARS-CoV-2-like viruses found in wildlife,the animal susceptibility to SARS-CoV-2,as well as the interspecies transmission risk of SARS-related coronaviruses(SARSr-CoVs)are gathered here.Finally,we discuss the strategies of how to be prepared against future outbreaks of emerging or re-emerging coronaviruses.

Dynamic variations in COVID-19 with the SARS-CoV-2 Omicron variant in Kazakhstan and Pakistan

Background The ongoing coronavirus disease 2019(COVID-19)pandemic caused by the severe acute respiratory syndrome-coronavirus 2(SARS-CoV-2)and the Omicron variant presents a formidable challenge for control and prevention worldwide,especially for low-and middle-income countries(LMICs).Hence,taking Kazakhstan and Pakistan as examples,this study aims to explore COVID-19 transmission with the Omicron variant at different contact,quarantine and test rates.Methods A disease dynamic model was applied,the population was segmented,and three time stages for Omicron transmission were established:the initial outbreak,a period of stabilization,and a second outbreak.The impact of population contact,quarantine and testing on the disease are analyzed in five scenarios to analysis their impacts on the disease.Four statistical metrics are employed to quantify the model’s performance,including the correlation coefficient(CC),normalized absolute error,normalized root mean square error and distance between indices of simulation and observation(DISO).Results Our model has high performance in simulating COVID-19 transmission in Kazakhstan and Pakistan with high CC values greater than 0.9 and DISO values less than 0.5.Compared with the present measures(baseline),decreasing(increasing)the contact rates or increasing(decreasing)the quarantined rates can reduce(increase)the peak values of daily new cases and forward(delay)the peak value times(decreasing 842 and forward 2 days for Kazakhstan).The impact of the test rates on the disease are weak.When the start time of stage Ⅱ is 6 days,the daily new cases are more than 8 and 5 times the rate for Kazakhstan and Pakistan,respectively(29,573 vs.3259;7398 vs.1108).The impact of the start times of stageⅢon the disease are contradictory to those of stageⅡ.Conclusions For the two LMICs,Kazakhstan and Pakistan,stronger control and prevention measures can be more effective in combating COVID-19.Therefore,to reduce Omicron transmission,strict management of population movement should be employed.Moreover,the timely application of these strategies also plays a key role in disease control.

Coexistence of multiple coronaviruses in several bat colonies in an abandoned mineshaft

Since the 2002–2003 severe acute respiratory syndrome(SARS) outbreak prompted a search for the natural reservoir of the SARS coronavirus, numerous alpha- and betacoronaviruses have been discovered in bats around the world. Bats are likely the natural reservoir of alpha- and betacoronaviruses, and due to the rich diversity and global distribution of bats, the number of bat coronaviruses will likely increase. We conducted a surveillance of coronaviruses in bats in an abandoned mineshaft in Mojiang County, Yunnan Province, China, from 2012–2013. Six bat species were frequently detected in the cave: Rhinolophus sinicus, Rhinolophus affinis, Hipposideros pomona, Miniopterus schreibersii, Miniopterus fuliginosus, and Miniopterus fuscus. By sequencing PCR products of the coronavirus RNA-dependent RNA polymerase gene(Rd Rp), we found a high frequency of infection by a diverse group of coronaviruses in different bat species in the mineshaft. Sequenced partial Rd Rp fragments had 80%–99% nucleic acid sequence identity with well-characterized Alphacoronavirus species, including Bt CoV HKU2, Bt CoV HKU8, and Bt CoV1,and unassigned species Bt CoV HKU7 and Bt CoV HKU10. Additionally, the surveillance identified two unclassified betacoronaviruses, one new strain of SARS-like coronavirus, and one potentially new betacoronavirus species. Furthermore, coronavirus co-infection was detected in all six bat species, a phenomenon that fosters recombination and promotes the emergence of novel virus strains. Our findings highlight the importance of bats as natural reservoirs of coronaviruses and the potentially zoonotic source of viral pathogens.

Longitudinal Surveillance of Betacoronaviruses in Fruit Bats in Yunnan Province,China During 2009–2016

Previous studies indicated that fruit bats carry two betacoronaviruses,BatCoV HKU9 and BatCoV GCCDC1.To investigate the epidemiology and genetic diversity of these coronaviruses,we conducted a longitudinal surveillance in fruit bats in Yunnan province,China during 2009–2016.A total of 59(10.63%)bat samples were positive for the two betacorona-viruses,46(8.29%)for HKU9 and 13(2.34%)for GCCDC1,or closely related viruses.We identified a novel HKU9 strain,tentatively designated as BatCoV HKU9-2202,by sequencing the full-length genome.The BatCoV HKU9-2202 shared 83%nucleotide identity with other BatCoV HKU9 stains based on whole genome sequences.The most divergent region is in the spike protein,which only shares 68%amino acid identity with BatCoV HKU9.Quantitative PCR revealed that the intestine was the primary infection organ of BatCoV HKU9 and GCCDC1,but some HKU9 was also detected in the heart,kidney,and lung tissues of bats.This study highlights the importance of virus surveillance in natural reservoirs and emphasizes the need for preparedness against the potential spill-over of these viruses to local residents living near bat caves.

Longitudinal surveillance of SARS-like coronaviruses in bats by quantitative real-time PCR

Dear Editor,The 2002–2003 severe acute respiratory syndrome coronavirus(SARS-CoV)(Drosten et al.,2003)caused human pandemics that began in China and spread globally.Subsequently,diverse SARS-like

Revolution of vitamin E production by starting from microbial fermented farnesene to isophytol

Vitamin E is one of the most widely used vitamins.In the classical commercial synthesis of vitamin E(a-tocopherol),the chemical synthesis of isophytol is the key technical barrier.Here,we establish a new process for isophytol synthesis from microbial fermented farnesene.To achieve an efficient pathway for farnesene production,Saccharomyces cerevisiae was selected as the host strain.First,b-farnesene synthase genes from different sources were screened,and through protein engineering and system metabolic engineering.

Genetic Evidence of Middle East Respiratory Syndrome Coronavirus(MERS-Cov) and Widespread Seroprevalence among Camels in Kenya

We describe the first genome isolation of Middle East respiratory syndrome coronavirus(MERS-CoV) in Kenya. This fatal zoonotic pathogen was first described in the Kingdom of Saudi Arabia in 2012. Epidemiological and molecular evidence revealed zoonotic transmission from camels to humans and between humans. Currently, MERS-CoV is classified by the WHO as having high pandemic potential requiring greater surveillance. Previous studies of MERS-CoV in Kenya mainly focused on site-specific and archived camel and human serum samples for antibodies. We conducted active nationwide cross-sectional surveillance of camels and humans in Kenya, targeting both nasal swabs and plasma samples from 1,163 camels and 486 humans collected from January 2016 to June 2018. A total of 792 camel plasma samples were positive by ELISA. Seroprevalence increased with age, and the highest prevalence was observed in adult camels(82.37%, 95%confidence interval(CI) 79.50–84.91). More female camels were significantly seropositive(74.28%, 95% CI 71.14–77.19)than male camels(P \ 0.001)(53.74%, 95% CI 48.48–58.90). Only 11 camel nasal swabs were positive for MERS-CoV by reverse transcription-quantitative PCR. Phylogenetic analysis of whole genome sequences showed that Kenyan MERSCoV clustered within sub-clade C2, which is associated with the African clade, but did not contain signature deletions of orf4 b in African viruses. None of the human plasma screened contained neutralizing antibodies against MERS-CoV. This study confirms the geographically widespread occurrence of MERS-CoV in Kenyan camels. Further one-health surveillance approaches in camels, wildlife, and human populations are needed.

Molecular detection of viruses in Kenyan bats and discovery of novel astroviruses, caliciviruses and rotaviruses

This is the first country-wide surveillance of bat-borne viruses in Kenya spanning from 2012–2015covering sites perceived to have medium to high level bat-human interaction. The objective of this surveillance study was to apply a non-invasive approach using fresh feces to detect viruses circulating within the diverse species of Kenyan bats. We screened for both DNA and RNA viruses;specifically, astroviruses(AstVs), adenoviruses(ADVs), caliciviruses(CalVs), coronaviruses(CoVs), flaviviruses, filoviruses, paramyxoviruses(PMVs), polyomaviruses(PYVs) and rotaviruses.We used family-specific primers, amplicon sequencing and further characterization by phylogenetic analysis. Except for filoviruses, eight virus families were detected with varying distributions and positive rates across the five regions(former provinces) studied. AstVs(12.83%), CoVs(3.97%), PMV(2.4%), ADV(2.26%), PYV(1.65%), CalVs(0.29%), rotavirus(0.19%) and flavivirus(0.19%). Novel CalVs were detected in Rousettus aegyptiacus and Mops condylurus while novel Rotavirus-A-related viruses were detected in Taphozous bats and R. aegyptiacus. The two Rotavirus A(RVA) strains detected were highly related to human strains with VP6 genotypes I2 and I16. Genotype I16 has previously been assigned to human RVA-strain B10 from Kenya only, which raises public health concern, particularly considering increased human-bat interaction.Additionally, 229E-like bat CoVs were detected in samples originating from Hipposideros bats roosting in sites with high human activity. Our findings confirm the presence of diverse viruses in Kenyan bats while providing extended knowledge on bat virus distribution. The detection of viruses highly related to human strains and hence of public health concern, underscores the importance of continuous surveillance.

Discovery of novel DNA viruses in small mammals from Kenya

Emergence and re-emergence of infectious diseases of wildlife origin have led pre-emptive pathogen surveillances in animals to be a public health priority.Rodents and shrews are among the most numerically abundant vertebrate taxa and are known as natural hosts of important zoonotic viruses.Many surveillance programs focused more on RNA viruses.In comparison,much less is known about DNA viruses harbored by these small mammals.To fill this knowledge gap,tissue specimens of 232 animals including 226 rodents,five shrews and one hedgehog were collected from 5 counties in Kenya and tested for the presence of DNA viruses belonging to 7 viral families by PCR.Diverse DNA sequences of adenoviruses,adeno-associated viruses,herpesviruses and polyomaviruses were detected.Phylogenetic analyses revealed that most of these viruses showed distinction from previously described viruses and formed new clusters.Furthermore,this is the first report of the discovery and full-length genome characterization of a polyomavirus in Lemniscomys species.This novel polyomavirus,named Ls Py V KY187,has less than 60%amino acid sequence identity to the most related Glis glis polyomavirus 1 and Sciurus carolinensis polyomavirus 1 in both large and small T-antigen proteins and thus can be putatively allocated to a novel species within Betapolyomavirus.Our findings help us better understand the genetic diversity of DNA viruses in rodent and shrew populations in Kenya and provide new insights into the evolution of those DNA viruses in their small mammal reservoirs.It demonstrates the necessity of ongoing pathogen discovery studies targeting rodent-borne viruses in East Africa.

Genetic Mutation of SARS-CoV-2 during Consecutive Passages in Permissive Cells

Dear Editor,The ongoing COVID-19 disease,caused by severe acute respiratory syndrome coronavirus 2(SARS-Co V-2),has led to over 112 million confirmed cases and 2.4 million deaths in more than 220 countries as of 25 February 2021(WHO 2021).Hospital-admitted patients show clinical features including fever,dry cough,fatigue,dyspnea,lymphopenia,and pneumonia with radiological groundglass lung opacities(Huang et al.2020;Guan et al.2020).SARS-Co V-2 was quickly isolated and could be detected in clinical samples,such as nasopharyngeal swabs,sputum,alveolar lavage fluid,and feces,as well as occasionally in seminal fluid and tears among other sources(Bhat et al.2020;Li et al.2020),which means that it can infect a variety of human tissues and organs.