A hybrid quantum computing pipeline for real world drug discovery.

Quantum computing, with its superior computational capabilities compared to classical approaches, holds the potential to revolutionize numerous scientific domains, including pharmaceuticals. However, the application of quantum computing for drug discovery has primarily been limited to proof-of-concept studies, which often fail to capture the intricacies of real-world drug development challenges. In this study, we diverge from conventional investigations by developing a hybrid quantum computing pipeline tailored to address genuine drug design problems. Our approach underscores the application of quantum computation in drug discovery and propels it towards more scalable system. We specifically construct our versatile quantum computing pipeline to address two critical tasks in drug discovery: the precise determination of Gibbs free energy profiles for prodrug activation involving covalent bond cleavage, and the accurate simulation of covalent bond interactions. This work serves as a pioneering effort in benchmarking quantum computing against veritable scenarios encountered in drug design, especially the covalent bonding issue present in both of the case studies, thereby transitioning from theoretical models to tangible applications. Our results demonstrate the potential of a quantum computing pipeline for integration into real world drug design workflows.

SFTSV infection in rodents and their ectoparasitic chiggers.

SFTSV, a tick-borne bunyavirus causing a severe hemorrhagic fever termed as severe fever with thrombocytopenia syndrome (SFTS). To evaluate the potential role of rodents and its ectoparasitic chiggers in the transmission of SFTSV, we collected wild rodents and chiggers on their bodies from a rural area in Qingdao City, Shandong Province, China in September 2020. PCR amplification of the M and L segments of SFTSV showed that 32.3% (10/31) of rodents and 0.2% (1/564) of chiggers (Leptotrombidium deliense) from the rodents were positive to SFTSV. Our results suggested that rodents and chiggers may play an important role in the transmission of SFTSV, although the efficiency of chiggers to transmit SFTSV needs to be further investigated experimentally.

Rickettsia japonica and Novel Rickettsia Species in Ticks, China.

PCR amplification indicated the minimum infection rate of Rickettsia spp. was 0.66% in Haemaphysalis longicornis ticks collected from Shandong Province, China. Phylogenetic analysis based on the rrs, gltA, ompA, and ompB genes indicated that the ticks carried R. japonica, Candidatus Rickettsia longicornii, and a novel Rickettsia species related to R. canadensis.

Anaplasma species detected in Haemaphysalis longicornis tick from China.

Anaplasma are tick-borne obligatory intracellular bacteria, which infect humans and other animals. The Anaplasma species carried by ticks in China are not well studied. We collected 3145 questing Haemaphysalis longicornis ticks including 120 larvae, 2460 nymphs and 565 adults from vegetation in Jiaonan County, Shandong Province, China from 2013 to 2015. All ticks were examined for the presence of Anaplasma species by nested PCR amplification of the 16S rRNA gene. For further differentiation of A. capra from A. centrale, gltA and msp2 genes were sequenced for A. capra. Three Anaplasma species were detected in the nymph and/or adult ticks with the minimum infection rate of ticks as follows: 1.55% for A. bovis, 0.10% for A. phagocytophilum, and 0.03% for A. capra. These results indicated that the H. longicornis tick in Jiaonan County carried multiple Anaplasma species, which may be a challenge for public health in the studying area.

Detection of a Novel Rickettsia From Leptotrombidium scutellare Mites (Acari: Trombiculidae) From Shandong of China.

Leptotrombidium scutellare mites, the vector of Orientia tsutsugamushi, have rarely been reported to associate with Rickettsia species. Three hundred nineteen chiggers were collected from the ears of 32 rodents captured in Huangdao District of Qingdao City, China, in October 2015. The chigger samples were tested for Rickettsia, severe fever with thrombocytopenia syndrome virus, and hantavirus by PCR or RT-PCR amplification. All mites were classified morphologically and molecularly as L. scutellare chiggers. Rickettsial DNA sequences were amplified for four genes including 16S rRNA, ompB, gltA, and 17 kD protein genes. The minimum infection rate (MIR; number of positive pools/total specimens tested) of the Rickettsia species in the chiggers were 2.8% (9/319). Phylogenetic analysis indicated that individual genes were closely related to different Rickettsia species including R. felis (with 16S rRNA gene), R. australis (with gltA gene), an unnamed Rickettsia sp. TwKM02 (with ompB gene), and Rickettsia endosymbiont of soft tick Ornithodoros erraticus (with 17 kD protein gene). Phylogenic analysis of the concatenated sequence of 16S rRNA, gltA, ompB, and 17 kD protein genes indicated that the Rickettsia species from L. scutellare chigger was most closely related to R. australis and R. akari. These results indicated that the Rickettsia species in chiggers was unique; it was named Candidatus Rickettsia leptotrombidium. Severe fever with thrombocytopenia syndrome virus and hantavirus were not amplified from the chiggers, suggesting lack of infection of these pathogens in the chiggers. A unique Rickettsia species was detected in L. scutellare, which expanded the knowledge on the vector distribution of Rickettsia.

Detection of Imjin Virus and Seoul Virus in Crocidurine Shrews in Shandong Province, China.

INTRODUCTION: Recently, hantaviruses have been discovered in insectivores in Europe, Asia, Africa, and North America. Imjin virus (MJNV) was first isolated from the lung tissues of Ussuri white-toothed shrew (Crocidura lasiura) from South Korea in 2009. We aim to detect the species and prevalence of insectivore- and rodent-borne hantaviruses in shrews and rodents. MATERIALS AND METHODS: Shrews and rodents were captured in Jiaonan County of Shandong Province, China, in 2014. RT-PCR was used to amplify viral RNA of Hantavirus species, including insectivore-borne Imjin virus (MJNV), rodent-borne Hantaan virus (HTNV), and Seoul virus (SEOV) from shrews and rodents. RESULTS AND DISCUSSION: We found that MJNV infected 10.7% (19/178) of Crocidura shrews, but it infected none of rodents (0/475); we also found that 2 of 178 (1.1%) Crocidura shrews were PCR positive to SEOV. This study indicated that the major animal hosts of Imjin virus are shrews, and rodent-borne SEOV can infect shrews.

Seroprevalence of Severe Fever with Thrombocytopenia Syndrome Virus in Hedgehog from China.

Severe fever with thrombocytopenia syndrome, an emerging hemorrhagic fever, is caused by severe fever with thrombocytopenia syndrome virus (SFTSV), a tick-borne bunyavirus. Information regarding SFTSV animal hosts is very limited. In this study, we showed that 64% (9/14) of hedgehogs in Shandong Province, China were seropositive to SFTSV antibody, suggesting that hedgehog could be a vertebrate parasitifer for SFTSV.

Prevalence of hemorrhagic fever with renal syndrome in Qingdao City, China, 2010-2014.

Hemorrhagic fever with renal syndrome (HFRS) was considered to be transmitted by Apodemus agrarius and Rattus norvegicus, the principal animal hosts of Hantaan virus and Seoul virus, respectively. The aim of this study is to determine the correlation of HFRS incidence with capture rate and hantavirus infection rate of rodent species in Qingdao City, China. We collected HFRS patients' information and captured field and residential rodents in Qingdao City, China from 2010 to 2014. The correlations of HFRS incidence to rodent capture rate and hantavirus infection rate of rodents were analyzed statistically. The main findings of this study are that the high HFRS incidence (19.3/100,000) is correlated to the capture rate of field Mus musculus (p = 0.011, r = 0.037); but surprisingly it did not correlated to the capture rate of the principal rodent hosts Apodemus agrarius and Rattus norvegicus and the hantavirus infection rate of these rodent species in the field or residential area. These novel findings suggest that Mus musculus, a nontraditional animal host of hantavirus may play an important role in hantavirus transmission in Qingdao City.

Detection of a Novel Ehrlichia Species in Haemaphysalis longicornis Tick from China.

We collected 2460 Haemaphysalis longicornis ticks from vegetation in Jiaonan County, Shandong Province, in June of 2013 and Daishan County, Zhejiang Province, China, in May of 2015. The tick DNA was subsequently amplified with nested polymerase chain reaction using Ehrlichia common 16S rRNA gene primers and Ehrlichia ewingii species-specific groEL and gltA primers. We found 0.4% (3/780) of the ticks from Zhejiang Province contained Ehrlichia DNA that was different from all known Ehrlichia species, but most closely related to E. ewingii. We concluded that a novel Ehrlichia species exists in H. longicornis ticks in China.

Haemaphysalis longicornis Ticks as Reservoir and Vector of Severe Fever with Thrombocytopenia Syndrome Virus in China.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever in East Asia caused by SFTS virus (SFTSV), a newly discovered phlebovirus. The Haemaphysalis longicornis tick has been suspected to be the vector of SFTSV. To determine whether SFTSV can be transmitted among ticks, from ticks to animals, and from animals to ticks, we conducted transmission studies between developmental stages of H. longicornis ticks and between ticks and mice. Using reverse transcription PCR, we also analyzed the prevalence of SFTSV infection among H. longicornis ticks collected from vegetation in Shandong Province, China. Our results showed a low prevalence of SFTSV among collected ticks (0.2%, 8/3,300 ticks), and we showed that ticks fed on SFTSV-infected mice could acquire the virus and transstadially and transovarially transmit it to other developmental stages of ticks. Furthermore, SFTSV-infected ticks could transmit the virus to mice during feeding. Our findings indicate ticks could serve as a vector and reservoir of SFTSV.

Prevalence of SFTSV among Asian house shrews and rodents, China, January-August 2013.

To evaluate the role of small mammals as hosts of severe fever with thrombocytopenia syndrome virus (SFTSV), we tested serum samples from rodents and shrews in China, collected in 2013. SFTSV antibodies and RNA were detected, suggesting that rodents and shrews might be hosts for SFTSV.