From a DENV-2 Screening Hit to Coverage of All Four Serotypes: Pan-Serotype Structure–Activity Relationship Optimization of JNJ-1802
From a DENV-2 Screening Hit to Coverage of All Four Serotypes: Pan-Serotype Structure–Activity Relationship Optimization of JNJ-1802
Introduction
Dengue virus (DENV) mainly comprises four serotypes: DENV-1, DENV-2, DENV-3, and DENV-4. All four serotypes can cause dengue virus infection, but their viral protein sequences are not identical, and the inhibitory activity of the same small molecule may differ substantially among serotypes. Therefore, the development of direct-acting antiviral agents against dengue requires consideration of whether a compound can simultaneously cover all four serotypes.
JNJ-1802 originated from a class of 3-acyl-indole inhibitors. In 2018, researchers identified this chemical series through a DENV-2 phenotypic antiviral screen and improved its antiviral activity through structure–activity relationship studies, while progressively achieving inhibitory activity against other serotypes. The optimization process also improved physicochemical properties and metabolic stability and revealed a clear difference in antiviral activity between the two enantiomers.[1]
Subsequent studies further expanded the evaluation to all four serotypes, different viral genotypes, chiral stability, and oral pharmacokinetic properties. JNJ-1802, reported in 2024, showed half-maximal effective concentration (EC₅₀) values of 0.057–11 nM against representative viruses from the four DENV serotypes, together with oral bioavailability in preclinical species, low clearance in human hepatocytes, and in vivo antiviral activity.[2,3]
The optimization of JNJ-1802 centered on a defined question: how can the same molecule maintain high antiviral activity against genetically diverse DENV viruses while also satisfying development-candidate requirements such as configurational stability, in vivo exposure, and safety?
Major Abbreviations and Symbols Used in This Article
Abbreviation or Symbol | Full Name or Meaning | Meaning in This Article |
DENV | Dengue virus | Virus studied in this article |
DENV-1–DENV-4 | Four major dengue virus serotypes | Used to evaluate pan-serotype drug coverage |
JNJ-1802 | Compound development code | Pan-serotype small-molecule inhibitor discussed in this article |
SAR | Structure–activity relationship | Relationship between changes in molecular structure and properties such as activity and stability |
EC₅₀ | Half-maximal effective concentration | Concentration required to achieve 50% antiviral effect; within the same assay system, a lower value generally indicates stronger activity |
NS3 | Nonstructural protein 3 | Has protease and helicase-related functions and participates in viral protein processing and RNA replication |
NS4B | Nonstructural protein 4B | Associated with the formation of membranous viral replication structures and is a key protein related to the activity of this inhibitor series |
V91A, etc. | Amino acid mutation notation | For example, V91A indicates substitution of valine (V) at position 91 by alanine (A) |
1. From a DENV-2 Hit to Evaluation of Activity Across All Four Serotypes
1.1 DENV-2 Phenotypic Screening Established the Chemical Starting Point
This series was initially identified through a DENV-2 phenotypic antiviral screen. Phenotypic screening directly measures whether a compound can inhibit viral replication in cells and does not require prior knowledge of a specific molecular target.
Early structural optimization initially focused on DENV-2. As data for the other three serotypes were incorporated, researchers found that the same compound did not exhibit identical activity across all four serotypes.[1]
SAR evaluation therefore needed to consider the following simultaneously:
DENV-1 EC₅₀｜DENV-2 EC₅₀｜DENV-3 EC₅₀｜DENV-4 EC₅₀
For a pan-serotype candidate, all four EC₅₀ values need to remain sufficiently low. The EC₅₀ against the relatively less sensitive serotype sets the lower limit of the molecule’s overall serotype coverage.
1.2 Activity Against All Four Serotypes Progressively Reached the Low-Nanomolar Range
Compound 24a, reported in 2023, showed EC₅₀ values of 1.1–240 nM across the four serotypes, while compound 28a showed values of 0.60–84 nM. Both also exhibited improved chiral stability and oral bioavailability in preclinical species.[2]
In 2024, JNJ-1802 achieved an EC₅₀ range of 0.057–11 nM against representative viruses from all four serotypes.[3]
Because the viral strains and assay systems differed among studies, activity improvements should not be calculated directly as fold changes across different publications. Taken together, the data from the successive stages show that later optimization shifted the effective concentrations required against different serotypes into lower concentration ranges.
Pan-serotype SAR therefore focuses on the overall activity distribution across the four serotypes and on whether relatively less sensitive serotypes can also retain high susceptibility to the compound.
2. NS4B and Viral Replication-Complex Assembly
2.1 NS3 and NS4B Participate in Viral RNA Replication
The DENV RNA genome is translated into a polyprotein that is subsequently cleaved into multiple mature viral proteins. NS3 and NS4B are both nonstructural proteins that are not incorporated into mature virions but participate in viral replication.
The N-terminal region of NS3 forms a serine protease with the assistance of NS2B, whereas its C-terminal region possesses nucleoside triphosphatase and RNA helicase activities. NS4B is a highly hydrophobic membrane-associated protein involved in endoplasmic reticulum membrane remodeling and the formation of viral RNA replication structures. Before maturation, NS4B is also present within the NS4A-2K-NS4B precursor, in which 2K is a short peptide connecting NS4A and NS4B.
Studies of JNJ-A07, a compound from the same series, first showed that this class of inhibitors can block interactions between NS3 and NS4B-related proteins and inhibit the formation of viral replication complexes.[4]
Subsequent experiments with JNJ-1802 produced results in the same direction. In a cellular system expressing the NS4A-2K-NS4B precursor and the NS2B–NS3 protease–helicase complex, JNJ-1802 reduced the formation of NS3–NS4B-related complexes.[5]
2.2 JNJ-1802 Primarily Affects the Formation of New Complexes
Time-dependent experiments further showed that JNJ-1802 prevents the formation of new NS3–NS4B-related complexes; when the relevant complexes had already been established before drug addition, the pre-existing complexes were not substantially disrupted.[5]
These results associate the action of JNJ-1802 with the assembly stage of the viral replication complex.
At the same time, NS4B resistance mutations markedly reduce viral susceptibility to JNJ-1802. In the original study, major resistance mutations including V91A, L94F, and T108I were all located in NS4B, and these mutations also increased the drug concentrations required to block the NS3–NS4B interaction.
The original Figure 1 brings these lines of evidence together in a single figure: from the chemical structure of JNJ-1802 and its in vitro activity against viruses from multiple serotypes and genotypes to NS4B resistance mutations and NS3–NS4B interaction experiments, illustrating the relationship among molecular structure—viral genetic diversity—NS4B-associated drug susceptibility.
Figure 1. Chemical structure of JNJ-1802, in vitro pan-genotype/pan-serotype antiviral activity, and NS4B-related mechanism of action.
(a) Chemical structure of JNJ-1802; (b) in vitro antiviral activity of JNJ-1802 in Vero E6 cells against clinical isolates covering different genotypes of DENV-1–DENV-4; (c) membrane topology of DENV NS4B and the major NS4B mutations selected during JNJ-1802 resistance selection; (d) concentration-dependent inhibition by JNJ-1802 of NS3–NS4B interactions involving wild-type and resistance-mutant proteins.
Image source: Original figure reproduced from Goethals O, Kaptein SJF, Kesteleyn B, et al. Blocking NS3–NS4B interaction inhibits dengue virus in non-human primates. Nature. 2023;615:678–686. DOI: 10.1038/s41586-023-05790-6, Figure 1. The original article is licensed under the Creative Commons Attribution 4.0 International License (CC BY 4.0).
Figure 1 also illustrates the evidentiary boundary of the current mechanistic interpretation. The 2023 study established that JNJ-1802 blocks the formation of NS3–NS4B-related complexes and that NS4B resistance mutations alter drug susceptibility, but at that time the specific atomic-level binding pose of JNJ-1802 with NS4B remained undetermined.[5] Therefore, subsequent SAR studies can establish whether a structural modification improves activity, but in the absence of a high-resolution complex structure, specific NS4B amino acid interactions cannot be assigned to each substituent.
3. SAR Optimization of Three Structural Regions of JNJ-1802
JNJ-1802 contains a defined stereogenic center and was selected as the (2S) configuration for development. Its structure can be divided into three major SAR regions:
① Methoxy/methylsulfonyl-substituted aniline moiety
② 4-Chloro-2-methoxyphenyl moiety attached to the stereogenic center
③ 5-Trifluoromethoxy-substituted indole moiety
The final structure resulted from continuous substituent scanning within these regions together with antiviral, metabolic, and pharmacokinetic data for the complete molecules.
3.1 Aniline Moiety: Modulation of Polarity and Metabolic Properties
The early 3-acyl-indole series already displayed high antiviral activity, but cellular activity alone does not guarantee adequate exposure after oral administration. The aniline region therefore became an important site for modulating molecular polarity and metabolic properties.
Researchers examined different polar side chains and sulfone substituents, and JNJ-1802 ultimately retained a methoxy- and methylsulfonyl-substituted aniline moiety.[3]
The methylsulfonyl group changes the polarity and hydrogen-bond-acceptor characteristics of this local structural region and can consequently influence the physicochemical and metabolic properties of the entire molecule. Experimental data for the final candidate showed that, in combination with the other two structural regions, this motif maintained high antiviral activity while providing oral bioavailability in preclinical species and low clearance in human hepatocytes.[3]
Optimization of the aniline moiety was therefore constrained simultaneously by antiviral potency, molecular polarity, metabolic stability, and in vivo exposure.
3.2 Chiral Aryl Group: Configurational Stability as a Development-Candidate Criterion
The central carbon atom of the 3-acyl-indole series can form two enantiomers. In the 2018 study, chiral chromatographic separation of racemic compounds revealed a clear difference in antiviral activity between the two enantiomers.[1]
This indicates that the three-dimensional arrangement around the stereogenic center affects productive molecular recognition. Subsequent optimization therefore required not only selection of the more active enantiomer but also sufficient configurational stability.
By 2023, chiral stability had already been incorporated into lead optimization together with pan-serotype activity and oral bioavailability.[2]
JNJ-1802 ultimately incorporated a 4-chloro-2-methoxyphenyl group at this position and was selected as the single (2S) configuration.
When the two enantiomers differ in antiviral activity, racemization of the active configuration changes the proportion of the genuinely more active molecular species. Chiral stability therefore affects maintenance of effective exposure to the more active enantiomer.
3.3 Substitution at the 5-Position of the Indole: Enhancing Pan-Serotype Potency
The indole aromatic ring represents another important SAR region in this series. Researchers evaluated different halogen, alkyl, and alkoxy substituents, and JNJ-1802 ultimately incorporated a 5-trifluoromethoxy (5-OCF₃)-substituted indole.
JNJ-1802 containing this final structural combination achieved EC₅₀ values of 0.057–11 nM against representative viruses from the four DENV serotypes.[3]
OCF₃ simultaneously alters the electronic properties, hydrophobicity, and steric volume of the aromatic ring, all of which may influence molecular conformation, target recognition, and metabolic behavior. Because an atomic-resolution JNJ-1802–NS4B complex structure is not available, what can currently be established is the experimental SAR: 5-OCF₃ is present in the final structural combination that achieved high-level pan-serotype activity, whereas its specific atomic-level mode of action requires further structural investigation.
Through continuous optimization of the aniline, chiral aryl, and indole regions, the final molecule achieved high pan-serotype antiviral activity together with configurational stability and suitable pharmacokinetic properties.
4. From Four Serotypes to Viral Genetic Diversity and In Vivo Efficacy
4.1 Genotypic Differences Remain Within the Same Serotype
DENV-1–DENV-4 are the four major serotypes, and each serotype contains multiple genotypes and naturally occurring viral strains.
JNJ-1802 was further evaluated against 20 DENV strains covering different genotypes across the four serotypes. Most strains showed mean EC₅₀ values of <0.04–1.8 nM, whereas one DENV-4 genotype 3 Thailand strain had a mean EC₅₀ of 45 nM.
Pan-serotype evaluation can therefore be progressively expanded as follows:
DENV-2 screening strain → representative strains from all four serotypes → multiple serotypes and multiple genotypes
The first level is suitable for rapid SAR screening; the second is used to determine whether there are obvious activity gaps among the four serotypes; and the third assesses the tolerance of a small molecule to naturally occurring viral genetic variation.
The relatively reduced susceptibility of the DENV-4 genotype 3 Thailand strain also shows that pan-serotype activity does not mean that all naturally occurring viral strains have identical susceptibility to the drug. A more accurate assessment is based on the overall distribution and range of EC₅₀ values across different viral strains.
4.2 In Vitro Activity Across All Four Serotypes Translates into In Vivo Efficacy in Mice
In vitro activity requires further validation through in vivo exposure and efficacy studies.
The original study first showed that JNJ-1802 reduced viral RNA in a dose-dependent manner in a DENV-2 AG129 mouse model and improved survival in a lethal infection model. The studies were subsequently expanded to DENV-1, DENV-3, and DENV-4.
Under a prophylactic dosing design, JNJ-1802 markedly reduced viral RNA levels in AG129 mice infected with DENV-1, DENV-3, or DENV-4. In the DENV-1, DENV-3, and DENV-4 infection models, both the 60 and 6 mg/kg/day prophylactic dosing groups showed clear survival benefits. The original study therefore concluded that these results extended the in vitro pan-serotype findings to mouse models representing all four serotypes.
Figure 2 presents this level of validation: coverage of all four serotypes was reflected not only in EC₅₀ values but also translated into reduced viraemia and improved survival in mouse models infected with different DENV serotypes.
Figure 2. In vivo antiviral activity of JNJ-1802 against all four DENV serotypes in AG129 mice.
(a,b) Design of the DENV-2 viraemia experiment and effects of different JNJ-1802 doses on viral RNA levels on day 3 after infection; (c,d) design of the lethal DENV-2 infection model and effects of different doses on mouse survival; in this model, an anti-flavivirus 4G2 antibody was administered before infection to induce antibody-dependent enhancement; (e) design of the viraemia/survival experiments for DENV-1, DENV-3, and DENV-4; (f–h) effects of JNJ-1802 on survival in mice infected with the three serotypes; (i–k) viral RNA levels on day 3 after infection.
Image source: Original figure reproduced from Goethals O, Kaptein SJF, Kesteleyn B, et al. Blocking NS3–NS4B interaction inhibits dengue virus in non-human primates. Nature. 2023;615:678–686. DOI: 10.1038/s41586-023-05790-6, Figure 2. The original article is licensed under CC BY 4.0. The original figure legend states that the experimental schematics in Figure 2a, 2c, and 2e were adapted from the earlier 2021 study by Kaptein et al. (reference [4] in this article).
Figure 2 primarily demonstrates in vivo efficacy across all four serotypes in mice. The original study also performed a separate therapeutic DENV-2 mouse experiment: viral RNA remained substantially reduced even when treatment was initiated on day 4 or day 5 after infection.[5]
Different genotypes reflect viral sequence differences already present in nature, whereas resistance-selection experiments reveal which mutations can reduce drug susceptibility under sustained drug pressure.
In two independent DENV-2 resistance-selection experiments, the first persistent NS4B mutation was V91A, indicating substitution of valine (Val, V) at position 91 by alanine (Ala, A). As drug pressure continued to increase, additional mutations including S85L, L94F, and T108I emerged.[5]
When these mutations were individually introduced into the viral replication assay system:
① V91A reduced JNJ-1802 activity by approximately 180-fold;
② L94F reduced activity by approximately 520-fold;
③ T108I reduced activity by approximately 12-fold;
④ The V91A/L94F/T108I triple-mutant combination reduced activity by approximately 4,200-fold.
These findings establish a relationship between changes in the NS4B sequence and changes in susceptibility to JNJ-1802.
The time required for resistance development also provides important information. V91A became persistent at approximately week 20. The virus then needed to accumulate additional NS4B mutations, and more than 40 weeks of culture were required before it could grow stably in the presence of 1.29 μM JNJ-1802, a concentration more than 20,000-fold higher than the EC₅₀ against the original virus.
The original study therefore characterized JNJ-1802 as having a relatively high genetic barrier to resistance.[5]
For pan-serotype candidates, high baseline potency also provides a degree of activity margin: when natural polymorphisms or resistance mutations reduce viral susceptibility, a lower starting EC₅₀ generally leaves more room for the molecule to retain effective inhibition.
6. Candidate Selection Depends on Both Antiviral Coverage and Drug-Like Properties
Selection of JNJ-1802 as a development candidate was based on multiple experimental dimensions.
The major properties reported in the 2024 Journal of Medicinal Chemistry study included:
① EC₅₀ values of 0.057–11 nM against representative viruses from all four DENV serotypes;
② oral bioavailability in multiple preclinical species;
③ low clearance in human hepatocytes;
④ no major alerts in in vitro safety pharmacology evaluation;
⑤ dose-dependent antiviral efficacy in a DENV-2 mouse infection model.[3]
The 2023 Nature study also noted that JNJ-A07, a compound from the same series, already exhibited high pan-serotype antiviral activity, but JNJ-1802 was preferentially selected for clinical development because of its improved preclinical safety profile.
These findings show that once in vitro antiviral activity reaches the low-nanomolar or even picomolar range, candidate evaluation becomes increasingly constrained by metabolic stability, oral exposure, configurational stability, and safety.
The development of JNJ-1802 shows that small-molecule optimization against genetically diverse viruses requires SAR evaluation at three levels.
The first level is the relationship between chemical structure and activity against a single viral strain.
This level is used to define the lead structure, identify modifiable molecular regions, and improve baseline antiviral potency.
The second level is the relationship between chemical structure and viral genetic diversity.
The same compound needs to progress from a single screening strain to all four serotypes and then further to different genotypes and naturally occurring viral strains. The distribution of EC₅₀ values across different strains reflects the extent to which a structure can accommodate naturally occurring viral sequence variation.
The third level is the integration of antiviral coverage with drug-like properties.
Once high potency has been achieved, chiral stability, metabolic clearance, oral exposure, in vivo efficacy, and safety collectively determine whether a molecule can become a development candidate.
JNJ-1802 evolved from a 3-acyl-indole lead identified through DENV-2 phenotypic screening into a candidate capable of covering all four DENV serotypes and multiple genotypes. The central feature of this process was the expansion of evaluation from activity against a single viral strain to the distribution of activity across viral genetic diversity, followed by verification that this coverage could be maintained in vivo and combined with pharmacokinetic and safety properties suitable for development.
This approach is also applicable to other antiviral drug-discovery programs involving substantial naturally occurring sequence variation: the sustained effectiveness of a candidate molecule depends not only on achieving the lowest EC₅₀ against a particular experimental strain, but also on the breadth of the viral genetic space it can cover and the antiviral activity margin it can retain in the face of natural variation and resistance mutations.
8. Representative Chemicals Related to JNJ-1802 Pan-Serotype SAR Optimization and Key Synthetic Studies
Table 1. Core Inhibitors and Building Blocks Related to Structure–Activity Relationship Studies
Category | CAS No. | Aladdin Catalog No. | Name | Specification or Purity | Product Features and Applications |
Enantiomeric control compound for mechanistic studies | 2135640-92-3 | (-)-JNJ-A07 | ≥99% | Low-activity enantiomeric control of JNJ-A07 for comparing the effects of stereochemical configuration on anti-DENV activity and NS4B-related mechanisms | |
Pan-serotype DENV inhibitor research compound | 2135640-93-4 | (+)-JNJ-A07 | ≥98% | Representative inhibitor from the same series as JNJ-1802 for studies of pan-serotype DENV activity, NS3–NS4B interactions, and replication-complex formation mechanisms | |
Indole-core reference building block | 120-72-9 | Indole | ≥99% | Basic heterocyclic core of 3-acyl-indole anti-DENV compounds for studies of indole substitution effects and structure–activity relationships | |
5-Halogen-substituted indole building block | 399-52-0 | 5-Fluoroindole | ≥98% | For investigating the effects of fluorine substitution at the indole 5-position on antiviral potency, electronic properties, and metabolic stability | |
5-Halogen-substituted indole building block | 17422-32-1 | 5-Chloroindole | ≥98% | For SAR studies of 5-chloro-substituted indoles and comparison of the effects of halogen size and electronic properties on activity | |
5-Alkyl-substituted indole building block | 614-96-0 | 5-Methylindole | ≥99% | For investigating the effects of small alkyl substitution at the indole 5-position on hydrophobicity, steric occupancy, and antiviral activity | |
5-Alkoxy-substituted indole building block | 1006-94-6 | 5-Methoxyindole | ≥99% | For comparing the electronic and polarity effects of alkoxy substitution at the indole 5-position in SAR studies of 3-acyl-indole series | |
Key JNJ-1802 indole building block | 262593-63-5 | 5-(Trifluoromethoxy)indole | ≥97% | Corresponds to the 5-trifluoromethoxyindole moiety of JNJ-1802 and can be used for structural optimization related to pan-serotype activity and synthesis of target compounds | |
Basic reference building block for aryl substitution | 93-25-4 | 2-Methoxyphenylacetic acid | ≥99% | Basic structural reference for the chiral aryl region, suitable for studying the effects of ortho-methoxy and subsequent para substitution on configurational stability and activity | |
Aryl halogen-substituted SAR building block | 886498-61-9 | 2-(4-Fluoro-2-methoxyphenyl)acetic acid | ≥98% | For synthesis of 4-fluoro-2-methoxyaryl series and investigation of the effects of para-fluorine substitution on pan-serotype activity and metabolic properties | |
Key JNJ-1802 aryl precursor | 170737-95-8 | 2-(4-Chloro-2-methoxyphenyl)acetic acid | ≥97% | Corresponds to the 4-chloro-2-methoxyphenyl region of JNJ-1802 and can serve as a key aryl acyl precursor for target-skeleton construction and aryl-substitution studies | |
Key JNJ-1802 aniline building block | 62606-02-4 | 3-Methanesulfonyl-5-methoxyaniline | ≥98% | Corresponds to the methoxy/methylsulfonyl-substituted aniline moiety of JNJ-1802 and is applicable to studies related to antiviral activity, molecular polarity, and metabolic properties |
Table 2. Key Reagents for JNJ-1802 Synthesis and Functional-Group Transformations
Category | CAS No. | Aladdin Catalog No. | Name | Specification or Purity | Product Features and Applications |
Reagent for acid chloride preparation | 7719-09-7 | T433841 | Thionyl chloride | Reagent grade, high purity, ≥99.5%, low iron | Used for conversion of arylacetic acids into the corresponding acid chlorides and for preparation of acyl precursors in the construction of 3-acyl-indole scaffolds |
Base for nucleophilic substitution reactions | 7087-68-5 | N,N-Diisopropylethylamine | Distillation grade, ≥99.5% | Sterically hindered organic base for nucleophilic substitution between α-halocarbonyl intermediates and substituted anilines and for acid scavenging in the reaction system | |
Indole acylation-activation reagent | 96-10-6 | D130049 | Diethylaluminum chloride | 1.0 M in hexanes | Lewis acid activation reagent that can promote Friedel–Crafts acylation at the 3-position of substituted indoles to construct the 3-acyl-indole core scaffold |
α-Bromination reagent | 4207-56-1 | Phenyltrimethylammonium tribromide | ≥97% | Mild brominating reagent for α-bromination of the side chain of 3-acyl-indoles, providing a reactive site for subsequent nucleophilic substitution with substituted anilines |
Note: The above are representative Aladdin products related to scientific research. Specific applications should be determined according to product specifications, batch COA, and the intended reaction or evaluation system. Additional information on product specifications, grades, and COAs can be searched on the Aladdin official website using the product name, CAS number, or catalog number.
References
[1] Bardiot, D.; Koukni, M.; Smets, W.; et al. Discovery of Indole Derivatives as Novel and Potent Dengue Virus Inhibitors. Journal of Medicinal Chemistry, 2018, 61(18), 8390–8401. DOI: 10.1021/acs.jmedchem.8b00913.
[2] Kesteleyn, B.; et al. Discovery of Acyl-Indole Derivatives as Pan-Serotype Dengue Virus NS4B Inhibitors. Journal of Medicinal Chemistry, 2023, 66(13), 8808–8821. DOI: 10.1021/acs.jmedchem.3c00403.
[3] Kesteleyn, B.; Bonfanti, J.-F.; Bardiot, D.; et al. Discovery of JNJ-1802, a First-in-Class Pan-Serotype Dengue Virus NS4B Inhibitor. Journal of Medicinal Chemistry, 2024, 67(5), 4063–4082. DOI: 10.1021/acs.jmedchem.3c02336.
[4] Kaptein, S. J. F.; Goethals, O.; Kiemel, D.; et al. A Pan-Serotype Dengue Virus Inhibitor Targeting the NS3–NS4B Interaction. Nature, 2021, 598, 504–509. DOI: 10.1038/s41586-021-03990-6.
[5] Goethals, O.; Kaptein, S. J. F.; Kesteleyn, B.; et al. Blocking NS3–NS4B Interaction Inhibits Dengue Virus in Non-Human Primates. Nature, 2023, 615, 678–686. DOI: 10.1038/s41586-023-05790-6.
For more related articles, see below:
Serological testing experiments
Serum collection and sterilization
Detection of soluble serum protein molecules (CBA)
D-DTTA Salts of Azaindole Chiral Amines: New Options for Chemical Splitting
The process path of EBL-3183: from indole to preclinical inhibitor
Base hydrolysis and activation experiments by diindolyl carbonyls