COVID-19 caused by SARS-CoV-2 was one of the most important pandemics of this century, and animal models have played a key role in helping to rapidly develop preventive vaccines and therapeutic drugs and to understand the pathogenesis and host immune response to SARS-CoV-2 infection.
Transmission of SARS-CoV-2 in humans occurs through direct contact, respiratory droplets, contaminated objects and aerosols, with a full genome length of approximately 29.8 kb and several open reading frames (ORFs). The first ORF (ORF1a/b) encodes a polyprotein (nsp1-nsp16) required for viral replication and transcription, and the remaining 13 ORFs encode auxiliary and structural proteins, including spines (S), membranes (M), envelopes (E), and nucleocapsids (N). Animal models play a crucial role in SARS-CoV-2 mechanism and therapeutics studies.
Clinical features of COVID-19
1. General clinical symptoms
Pneumonia and other concomitant symptoms are the typical presentation of patients with SARS-CoV-2 infection. Fever (more than 90%) and cough (more than 80%) were the most prevalent symptoms. Various viral variations result in varied clinical signs, different morbidity, and different mortality in particular subpopulations.
2. Occurrence of infection in different populations
Acute respiratory distress syndrome, hospitalization, and mortality were more likely to result from severe or critical illnesses in elderly people with underlying chronic conditions. Fever (7/9), cough (4/9), myalgia (3/9), sore throat (2/9), diarrhea (1/9), and respiratory distress (1/9) are symptoms that pregnant women with SARS-CoV-2 infection present with. There are gender disparities in the severity of COVID-19, and childhood infections make up about 15% of all cases. Clinical manifestations of COVID-19 include skin lesions as well as respiratory, gastrointestinal, and neurological problems. It seems that males are more likely than females to have COVID-19 infection.
Receptors and cellular proteases mediating SARS-COV-2 infection
1. Classical receptors and new candidate receptors
ACE2 is the most widely recognized receptor for SARS-CoV-2. CD147-prickle protein interaction is a pathway for SARS-CoV-2 infection of host cells. ASGR1 mediates the internalization of galactose-terminated glycoproteins into hepatocytes and their degradation in lysosomes. Genomic receptor profiling identified ASGR1 and KREMEN1 as possible alternative functional receptors for SARS-CoV-2 entry into cells. SARS-CoV-2 infection promotes liver injury through pathways that may be influenced by previous pathological states and hepatic expression of NRP1. DPP4, AGTR2, ANPEP, and ENPEP are candidate receptors for SARS-CoV-2 infection.
2. Proteases mediating the entry of SARS-CoV-2 virus
A crucial part of SARS-CoV-2 infection and cell invasion is played by TMPRSS2. Key proteases enabling SARS-CoV-2 entrance into HEK 293/hACE2 cells are histone proteases B and L. The ability of the endogenous serine protease furin to cleave S proteins increases SARS-CoV-2 binding affinity for ACE2 receptors. Serine endopeptidase trypsin may be one of the proteases that contribute to SARS-CoV-2 entry. Other common host factors such as CSNK2B, GDI2, SLC35B2, DDX51, VPS26A, ARPP-19, C1QTNF7, ALG6, LIMA1, COG3, COG8, BCOR, LRRN2, and TLR9 may also regulate SARS-CoV-2 infection.
COVID-19 animal model
1. NHP
Non-human primates (NHPs) share significant similarities with humans in terms of physiological characteristics and immune regulation and have been intensively utilized to develop COVID-19 disease models. Rhesus monkeys are the most commonly used model of COVID-19 disease, but NHPs are facing great demand and soaring costs, so it may be necessary to find alternative models.
2. Mouse model
* Stably inherited transgenic mouse model.
Stably inherited transgenic mouse models expressing hACE2 resulted in SARS-CoV-2 susceptibility and could be used for preclinical evaluation of vaccines and drugs. Impaired lung function was observed in certain HFH4-hACE2 and K18-hACE2 mouse models of infection, with more efficient viral replication and severe disease manifestations in older mice.
Differences in hACE2 expression patterns in SARS-CoV-2 mouse models with different SARS-CoV-2 strains and different routes of infection and viral doses lead to different clinical manifestations and pathological changes.
* Mouse models of sensitization by Ad5-hACE2 or AAV-hACE2 transduction
Mice transduced in the adeno-trachea using an adeno-associated vector expressing hACE2 or adenovirus 5 (AAV-hACE2, Ad5-hACE2) resulted in hACE2 expression in lung tissue, allowing viral entry and infection.
* A model based on mouse-adapted SARS-CoV-2 strains
Intranasal inoculation of young mice with lung homogenates after SARS-CoV-2 infection of BALB/c mice produces mouse-adapted virus strain WBP-1. WBP-1 exhibits higher infectivity in BALB/c. Accumulation of mutations by successive passages and precise reverse genetic techniques allow the establishment of mouse-adapted strains.
* Humanized mouse models established with transplanted human tissue or cells
The SCID-hu lung mouse model and the recently established mouse model co-transplanted with human fetal lung tissue and myeloid-enhanced human immune system.
3. Syrian hamster model
Hamsters infected with SARS-CoV-2 develop respiratory and pulmonary disease and long-term damage to other physiological systems, and viral loads can be detected in the respiratory tract. Close contact transmission models have also been tested in hamsters, indicating that co-housing contact with hamsters carrying SARS-CoV-2 is an effective way to transmit the disease.
4. Ferret and mink models
Ferrets and mink, both members of the ferret family, are highly susceptible to several human respiratory viruses. After infection with SARS-CoV-2, ferrets exhibit common clinical signs and pathological examinations show varying degrees of lung damage. The prominent use of ferrets and mink is for transmission studies.
5. Poultry and livestock
Cats, dogs, chickens, pigs, and ducks can undergo SARS-CoV-2 infection but do not exhibit clinical signs, suggesting that an in vivo model may not be appropriate. Infection of sheep supports only limited viral replication, which can occur via respiratory droplets or aerosols.
According to the report published by Allied Market Research, the global biotech ingredients market was pegged at $51.3 billion in 2020 and is estimated to hit $75.3 billion by 2028, registering a CAGR of 4.8% from 2021 to 2028.
The report provides an in-depth analysis of the top investment pockets, top winning strategies, drivers & opportunities, market size & estimations, competitive landscape, and changing market trends.Shift in consumer preference from synthetic to bio-based ingredients and development in biotechnology fuel the growth of the global biotech ingredients market.
On the other hand, limited availability of raw materials restrains the growth to some extent.
However, favorable government policies and technological advancements in bio-engineering are expected to create lucrative opportunities in the industry.Request PDF Brochure: https://www.alliedmarketresearch.com/request-sample/11710COVID-19 scenario-The outbreak of the pandemic has given way to either closure or suspension of production activities in most industrial units across the globe, which has impacted the market negatively.Nevertheless, initiation of mass vaccination in most countries is projected to mend the global situation and market is expected to get back on track soon.The global biotech ingredients market is analyzed across type, product, expression systems, and region.
The biosimilars segment, on the other hand, would exhibit the fastest CAGR of 5.0% during the forecast period.Based on product, the monoclonal antibodies segment contributed to more than one-fifth of the total market revenue in 2020 and is expected to dominate by 2028.
However, the hormones and growth factors segment would cite the fastest CAGR of 5.5% during from 2021 to 2028.Get Detailed COVID-19 Impact Analysis on the Biotech Ingredients Market: https://www.alliedmarketresearch.com/request-for-customization/11710?reqfor=covidBased on region, Europe held the major share in 2020, garnering nearly two-fifths of the global market.
