Drug Discovery Services for SARS-CoV-2

Antiviral Drug Discovery for SARS-CoV-2

High-throughput Screening (HTS) Services of SARS-CoV-2 Drug Candidates

HTS has made significant contributions to early-stage drug development. By screening large and entire libraries (e.g., combinatorial chemistry, genomics, protein, and peptide libraries) directly against the drug target, we can reveal several promising drug candidates to accelerate drug discovery.

Broad-spectrum SARS-CoV-2 Antiviral Drug Discovery Services

Antiviral drugs with broad-spectrum activities have been shown to significantly simplify the treatment of CoV infection. Therefore, the development of highly effective, broad-spectrum antiviral agents is a long pursued goal shared by the fields of virology and pharmaceutics. Interferon (α and β) is the most common antiviral drug with broad-spectrum efficiency.

Nucleoside Analogue Inhibitors

Nucleoside analog inhibitors are dNTPs or rNTPs that lack 3'-OH group. They have been a class of drug candidates with the potential for potent inhibition of CoV. These antiviral agents play an antiviral role through inhibition of RNA synthesis during viral replication.

Protease Inhibitors

Viral proteases act as essential regulators in CoV replication, so both proteases are considered attractive targets for antiviral therapeutics. It has been documented that protease inhibitors can effectively block the replication of SARS-CoV and MERS-CoV, provide a promising foundation for the development of protease inhibitors drug to block SARS-CoV-2.

Neutralizing Antibody Development

Neutralizing antibodies (nAbs) could be used in an outbreak setting for the prophylaxis and early treatment of emerging viral pathogens. In view of SARS-CoV-2, its structural spike proteins (S) are key to the infectivity and pathogenicity, indicating their great promise as an effective target of neutralizing antibodies.

Inhibitor of Host Cell Protease

Viral S-protein is often activated for fusion by host protease processing which is essential for the viral life cycle. So, host cell proteases have been recognized as critical determinants of coronavirus tropism and pathogenesis. Targeting host cell proteases has attracted numerous research efforts to develop antiviral drugs used against coronavirus infections safely and effectively.

Neuraminidase Inhibitors (NAIs)

NAIs are a class of antiviral agents that bind to the neuraminidase of the virus and prevent its cleavage, thus inhibiting the release of new virus particles. Commonly used as antiviral drugs in the clinic, neuraminidase inhibitors could be the drug treatment options for SARS-CoV-2.

Antiviral Peptide

Viral S-proteins attach to cell receptors, undergo proteolytic cleavage, and then refold in a process that catalyzes virus-cell membrane fusion, finally promotes the entry of CoV. Fusion-inhibiting peptides bind to S proteins and act as antiviral peptides to interfere with refolding, and prevent infection.

Abelson Kinase Inhibitors

Abelson (Abl) kinase inhibitor, such as imatinib, has been revealed to significantly reduce SARS-CoV and MERS-CoV viral titers and prevents endosomal entry. The membrane fusion (both virus-cell and cell-cell) is blocked in the presence of Abl kinase inhibitors, suggesting the potential as a promising drug for the treatment of emerging of SARS-CoV-2.

RNA Synthesis Inhibitors

RNA synthesis inhibitors impede the formation of double membrane vesicles (DMVs), a hallmark of coronavirus replication. Therefore, they have broad antiviral activity against diverse coronaviruses, such as highly pathogenic SARS-CoV and MERS-CoV.

Anti-inflammatory Drugs

anti-inflammatory drugs (such as hormones and other molecules) are a front-line treatment in the clinic and prophylactic for SARS-CoV-2 infection. Several nonsteroidal anti-inflammatory drugs (NSAIDs) potently inhibit the entry of virus.

Complement Therapy

Finding targets from the complement system is one of the important directions to the treatment of SARS-CoV-2-caused inflammatory factor storm

SARS-CoV-2 aptamers can be used to quickly establish effective detection methods, and may also be used for the treatment of COVID-19.

By suppressing the expression of the host factors essential to the infection of these viruses, the immune escape of the virus due to mutation can be avoided.

Vaccine Discovery Services for SARS-CoV-2

In Silico Vaccine Design

In silico identification of potential epitopes present in SARS-CoV-2 proteins is essential for vaccine design and putative drug development for treatment against viral infection. In vaccine design, databases and in silico tools play different but complementary roles.

Live Attenuated and Killed Vaccine

Scientists have shown that targeting the CoV conserved 2’O MTase in parallel with other conserved attenuating mutations is a promising strategy to generate live-attenuated and killed vaccine strains against current and future CoVs.

Recombinant Subunit Vaccine

Subunit vaccines usually include only the components, or antigens of virus, that best stimulate the immune system. Monomeric and trimeric recombinant SARS-CoV S protein subunit vaccine candidates showed complete protection in mice.

mRNA Vaccine

mRNA vaccines represent a promising alternative to conventional vaccine approaches by introducing an mRNA sequence encoding the antigen. With the technological advances, mRNA vaccines have largely overcome issues with the instability of mRNA and the difficulty of delivering it into cells.

DNA Vaccine

Compared with traditional protein/peptide vaccines that induce antigen-specific immune responses, DNA vaccines are more stable, more economical, easier to produce, and safer.

Modified Vaccinia Virus Vectored Vaccine

Modified vaccinia virus Ankara (MVA) is an attenuated derivative vector for human applications due to its strong safety profile and immunogenicity in vivo. It now has been developed as a recombinant viral vector to produce vaccines against infectious diseases, such as CoVs infection.

Virus-Like Particles Based Vaccine

Virus-like particles (VLPs) are noninfectious multiprotein structures, based on which, scientists have developed VLPs-based vaccines as one of the most exciting emerging vaccine technologies for generating effective and long-lasting protection in infectious diseases.

Formulation Optimization Platform

Vaccine formulation is complex and should be tightly regulated. Vaccine formulation and optimization platform provides efficient antigens and immunomodulators for both vaccine potency and safety profiles.

Analysis & Qualification

Vaccine analysis and qualification services can help determine vaccine's purity, impurity, potency, and quantity. It's an important part of vaccine development.

Evaluation Platforms for SARS-CoV-2 Drugs

Reverse Genetics Systems

Reverse genetics systems are capable of generating specific viruses, including coronavirus, which have been applied in target screening and drug discovery. Furthermore, reverse genetics systems are critical to studying the lifecycle of different viruses without a large-scale containment laboratory.

Cell Lines

Creative Biolabs has developed a series of cell lines for COVID-19 research, including ACE2-enhanced or knockout (KO) cell lines, TMPRSS2-enhanced or knockout (KO) cell lines, and so on.

Spike-pseudovirus Based Neutralization Assay

Creative Biolabs packages a pseudovirus with the SARS-CoV-2 spike protein on the surface and a luciferase reporter gene inside, and uses the proprietary ACE2-CHO Clonal Cell-expressing the ACE-2 receptor as the target cell, which can effectively assess the neutralizing activity of the COVID-19 vaccine or drug.

Protease Inhibitor Assay

To find and validate potent inhibitors for SARS-CoV-2 protease, Creative Biolabs provides protease assay service to help speed up the development of therapeutics to conquer COVID-19.

Animal Models

Creative Biolabs offers high-quality animal model development services to accelerate the drug discovery process for the treatment of coronavirus infection.

Cytokine and Chemokine Responses Study

Creative Biolabs offers various animal models, such as mice, rats, dogs, and transgenic mice, to overcome the hurdle for investigating the cytokine and chemokine responses of SARS-CoV-2. Additionally, we have also established a panel of pre-qualified cytokine and chemokine assays to avoid a number of additional diseases, including acute lung injury (ALI), and acute respiratory distress syndrome (ARDS), caused by SARS-CoV-2 targeted new drugs.